A Comprehensive Review of the Classification, Sources, Phytochemistry, and Pharmacology of Norditerpenes

Abstract

Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and α-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.

1. Introduction

Diterpenes are natural terpenes composed of twenty carbon atoms in their molecules and are formed by the polymerization of four isoprene units. They are widely distributed in plants, particularly in plant-secreted milk and resin. In addition to plants, diterpenes can also be found in fungal metabolites and marine organisms. Generally consisting of 20 carbons, diterpenes can give rise to norditerpenes with fewer carbon atoms due to the absence of one to three carbon atoms within the diterpene core structure. C19 norditerpenes, which lack one carbon atom, represent the most common structural type among norditerpenes. Natural sources of norditerpenes exhibit diverse pharmacological activities including anti-inflammatory, anti-tumor, and antimicrobial effects. Therefore, extensive attention has been drawn toward research on norditerpenes. Norditerpene alkaloids are a class of norditerpenes. Yong Shen and coworkers reviewed 337 naturally occurring diterpene alkaloids, including 251 norditerpene alkaloids, derived from studies published between 2008 and 2018 [1]. To avoid the duplication of previous work, this article reviews the structural types and biological activities of norditerpenes (norditerpene alkaloids are not included) derived from studies published between 2010 and 2023. In general, 557 norditerpenes and their derivatives were found in the natural world, distributed into 132 species and 51 families (Table 1). This provides the basis for further research on the discovery of natural product drugs.

Table 1.

Sources of 557 norditerpenes (families, genera, and species and the corresponding quantity of the compounds).

Family	Genus	Species	Quantity of Norditerpenes
Lamiaceae (143)	Callicarpa	Callicarpa integerrima	2
	Teucrium	Teucrium viscidum	3
	Sideritis	Sideritis pullulans	2
	Leucas	Leucas zeylanica	2
	Isodon	Isodon rubescens	4
		Isodon eriocalyx	1
		Isodon pharicus	1
		Isodon phyllostachys	2
		Isodon rosthornii	1
		Isodon ternifolius	1
	Salvia	Salvia aethiopis	1
		Salvia deserta	5
		Salvia miltiorrhiza	26
		Salvia mirzayanii	1
		Salvia grandifolia	4
		Salvia leriifolia	1
		Salvia yunnanensis	3
		Salvia digitaloides	17
		Salvia rhytidea	3
		Salvia sahendica	1
		Salvia castanea	4
		Salvia przewalskii	5
	Perovskia	Perovskia abrotanoides	17
		Perovskia atriplicifolia	6
Euphorbiaceae (75)	Croton	Croton cajucara	1
		Croton haumanianus	1
		Croton yanhuii	4
		Croton euryphyllus	7
		Croton caudatus	2
		Croton cascarilloides	2
		Croton crassifolius	4
	Flueggea	Flueggea acicularis	5
		Flueggea virosa	2
	Baccaurea	Baccaurea ramiflora	4
	Jatropha	Jatropha podagrica	2
	Trigonostemon	Trigonostemon chinensis	11
		Trigonostemon flavidus	4
		Trigonostemon howii	1
	Malpighia	Malpighia emarginata	3
	Phyllanthus	Phyllanthus flexuosus	1
	Drypetes	Drypetes perreticulata	4
	Aleurites	Aleurites moluccanus	2
	Euphorbia	Euphorbia neriifolia	6
		Euphorbia royleana	1
		Euphorbia ebracteolata	4
		Euphorbia dracunculoides	2
Cephalotaxaceae (66)	Cephalotaxus	Cephalotaxus sinensis	8
		Cephalotaxus fortunei	56
		Cephalotaxus mannii	2
Celastraceae (20)	Euonymus L.	Euonymus verrucosus var. pauciflorus	3
		Euonymus grandiflflorus Wall	1
	Maytenus	Maytenus senegalensis	1
	Celastrus	Celastrus angulatus	9
		Celastrus orbiculatus	4
	Tripterygium	Tripterygium wilfordii	2
Icacinaceae (16)	Icacina	Icacina trichantha	16
Orchidaceae (16)	Flickingeria	Flickingeria fimbriata	16
Podocarpaceae (14)	Podocarpus	Podocarpus nagi	9
		Podocarpus macrophyllus	5
Pinaceae (13)	Abies	Abies forrestii	2
	Pinus	Pinus yunnanensis	1
		Pinus banksiana Lamb	1
	Pseudotsuga	Pseudotsuga sinensis	9
Picrodendraceae (12)	Austrobuxus	Austrobuxus carunculatus	12
Taxaceae (11)	Amentotaxus	Amentotaxus argotaenia	11
Compositae (10)	Eupatorium	Austroeupatorium inulifolium	10
Chloranthaceae (9)	Chloranthus	Chloranthus serratus	2
		Chloranthus sessilifolius	7
Asteraceae (8)	Grazielia	Grazielia gaudichaudeana	3
	Wedelia	Wedelia trilobata	1
	Stevia	Stevia rebaudiana	3
	Baccharis	Baccharis retusa	1
Zingiberaceae (8)	Amomum	Amomum maximum	2
		Amomum villosum	1
	Hedychium	Hedychium forrestii	3
	Elettaria	Elettaria cardamomum	2
Salicaceae (7)	Populus	Populus euphratica	7
Araucariaceae (5)	Agathis	Agathis macrophylla	5
Leguminosae (5)	Erythrophleum	Erythrophleum fordii	2
		Erythrophleum suaveolens	1
	Caesalpinia	Caesalpinia decapetala var. japonica	1
		Caesalpinia minax	1
Menispermaceae (5)	Tinospora	Tinospora capillipes	5
Annonaceae (4)	Annona	Annona squamosa L.	2
	Polyalthia	Polyalthia longifolia	2
Dipterocarpaceae (4)	Resina	Resina Commiphora	4
Pallaviciniaceae (4)	Pallavicinia	Pallavicinia ambigua	4
Scrophulariaceae (4)	Scrophularia	Scrophularia dentata	4
Alangiaceae (2)	Alangium	Alangium chinense (Lour.) Harms	2
Botryosphaeriaceae (2)	Diplodia	Diplodia olivarum	2
Caprifoliaceae (2)	Viburnum	Viburnum odoratissimum	2
Ditrichaceae (2)	Ceratodon	Ceratodon purpureus	2
Malpighiaceae (2)	Aspidopterys	Aspidopterys obcordata	2
Paeoniaceae (2)	Paeonia	Paeonia veitchii	2
Rosaceae (2)	Crataegus	Crataegus pinnatifida	2
Thymelaeaceae (2)	Aquilaria	Chinese eaglewood	2
Apiaceae (1)	Azorella	Azorella compacta	1
Cupressaceae (1)	Thuja	Thuja orientalis	1
Ericaceae (1)	Lyonia	Lyonia ovalifolia	1
Pentaphylacaceae (1)	Adinandra	Adinandra poilanei	1
Ranunculaceae (1)	Trollius	Trollius chinensis	1
Eurotiaceae (35)	Penicillium	Penicillium oxalicum	1
		Penicillium sp. DT10	1
		Penicillium thomii	1
	Aspergillus	Aspergillus taichungensis	4
		Aspergillus aculeatinus	1
		Aspergillus sp. YXf3	1
		Aspergillus wentii EN-48	26
Discellaceae (14)	Oidiodendron	Oidiodendron truncatum	14
Dematiaceae (3)	Alternaria	Alternaria brassicicola	3
Thermomonosporaceae (2)	Actinomadura	Actinomadura sp. KC 191	2
Carboniaceae (1)	Xylaria	Xylaria longipes	1
Moniliaceae (1)	Trichoderma	Trichoderma citrinoviride	1
Cortinariaceae (1)	Cortinarius	Cortinarius pyromyxa	1
Alcyonidae (30)	Sinularia	Sinularia scabra	16
		Sinularia maxima	3
		Sinularia nanolobata	1
		Sinularia siaesensis	1
		Sinularia hirta	2
		Sinularia densa	7
Choiidae (9)	Spongia	Spongia officinalis	2
	Dendrilla	Dendrilla antarctica	2
	Cacospongia	Cacospongia sp.	5
Xeniidae (5)	Cespitularia	Cespitularia taeniata	2
		Cespitularia sp.	3
Chromodorididae (3)	Goniobranchus	Goniobranchus Mollusks	3
Gorgoniaceae (1)	Junceella	Junceella fragilis	1
Anthoptilidae (1)	Anthoptilum	Anthoptilum grandiflflorum	1
Loliginidae (1)	Uroteuthis	Uroteuthis (Photololigo) duvaucelii	1
Veneridae (1)	Paphia	Paphia malabarica	1
Amber (1)	-	Dominican amber	1

2. Chemical Constituents of C19 Norditerpenes

In nature, seven primary categories of C19 norditerpenes have been identified: the labdane, pimarane, abietane, kaurane, clerodane, cephalotane, and cembranoid types. These types are shown in Figure 1 as their fundamental frameworks. Additionally, there are other norditerpenes with distinctive structures in the natural environment.

Figure 1.

Basic skeleton of C19 norditerpenes.

2.1. Labdane

Labdane norditerpenes are commonly found as bicyclic diterpenes, with a trans-fused A/B ring in the nuclear parent and a side chain typically consisting of a six-carbon open chain. The presence of hydroxyl groups on the side chain allows for easy dehydration and condensation reactions, leading to the formation of a five-membered ring. Labdane-type diterpenes with both an open-chain structure and a five-membered ring in the side chain have a wide distribution (Table 2, Figure 2).

Table 2.

Chemical constituents of labdane-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
1	penioxalicin	P. oxalicum	-	[2]
2	penitholabene	P. thomii	-	[3]
3	euonymupene C	E. verrucosus	twigs	[4]
4	euonymupene A	E. verrucosus	twigs	[4]
5	3β-hydroxy-15-nor-14-oxo-8(17),12-labdadien-14-al	C. serratus	whole plants	[5]
6	3β,6β-dihydroxy-15-nor-14-oxo-8(17),12-labdadien-14-al	C. serratus	whole plants	[5]
7	15-nor-14-oxolabda-8(17),12E-dien-19-oic acid	A. macrophylla	aerial parts	[6]
8	15-nor-14-oxolabda-8(17),13(16)-dien-19-oic acid	T. orientalis	leaves and stems	[7]
9	grazielabdane A	G. gaudichaudeana	aerial parts	[8]
10	grazielabdane B	G. gaudichaudeana	aerial parts	[8]
11	grazielabdane C	G. gaudichaudeana	aerial parts	[8]
12	austroeupatol	A. inulifolium	aerial parts	[9,10]
13	inulifolinone A	A. inulifolium	leaves	[9,10]
14	inulifolinone B	A. inulifolium	leaves	[9,10]
15	inulifolinone C	A. inulifolium	leaves	[9,10]
16	inulifolinone D	A. inulifolium	leaves	[9,10]
17	inulifolinone E	A. inulifolium	leaves	[9,10]
18	inulifolinone F	A. inulifolium	leaves	[9,10]
19	inulifolinone I	A. inulifolium	leaves	[9,10]
20	inulifolinone G	A. inulifolium	leaves	[9,10]
21	inulifolinone H	A. inulifolium	leaves	[9,10]
22	amomaxin B	A. maximum	roots	[11]
23	amomaxin A	A. maximum	roots	[11]
24	hedychin E	H. forrestii	rhizomes	[12]
25	pallambin A	P. ambigua	-	[13]
26	pallambin B	P. ambigua	-	[13]
27	pallambin C	P. ambigua	-	[13]
28	pallambin D	P. ambigua	-	[13]

Figure 2.

Structures of labdane-type C19 norditerpenes.

Compound 1 is a novel diterpene belonging to the 3-nor-2,3-seco-labdane class. It is characterized by fission the between C-2 and C-3 of ring A, followed by decarboxylation at C-3. Compound 2 is a rare 19-nor labdane-type diterpene isolated from fungus, while compounds 3–8 possess a fused bicyclic fragment with a 6/6 fusion, both of which are classified as 15-norditerpenes. Compounds 9–21 belong to the ent-nor-furano diterpene of the labdane series. Compounds 22–23 feature unique nine-membered ring structures, showcasing unprecedented characteristics. Compound 23 exhibits an exceptional structural motif with a fused α, β-unsaturated-γ-lactone unit, and a nine-membered ring B at C-10/C-11. Compound 24 represents a rare instance of a 6-norlabdane-type diterpene containing a tetrahydrofuran-lactone moiety. Compounds 25–26 display unparalleled hexacyclic structures as 19-nor-secolabdane diterpenes with tetracyclodecane skeletons. Compounds 27–28 are structurally similar to compounds 25–26 and exist as Z(E)-isomers.

2.2. Clerodane

Clerodane norditerpenes consist of a fused-ring decalin moiety (C₁–C₁₀) and a six-carbon side chain at C-9. Based on the A/B ring junction configuration and the substituents on C-8 and C-9, its skeletons can be classified into four types (Figure 3).

Figure 3.

Basic skeletons of clerodane-type C19 norditerpenes.

Compound 29 is characterized by a double bond between carbon atoms C-3 and C-4. Compounds 30–31 have a fused tricyclic ring system with a 6/6/6 configuration. Compound 32 belongs to the bioactive clerodane class of 19-nor-diterpenes, featuring a cyclohexenone decalin ring. Compound 33 is a dehydrogenated derivative of compound 34, resulting in the removal of hydrogen atoms from positions C₁₁–C₁₂. Compounds 35–37 exhibit a distinct 3,5(10)-diene moiety. Compounds 38–40 belong to the furanoditerpenes of the 18-nor-clerodane class. Compounds 43–44 display an opened lactone ring at positions 17 and 12, accompanied by oxidation occurring at position C-12. Compounds 43–52 possess a butenolide moiety extending from C-19 to C-6. Compound 53 demonstrates a similar structure, albeit featuring a double bond between C-5 and C-10. Compound 54 consists of a unique cage-like tetracyclic ring system, fused in a pattern of 6/6/6/5, which is formed by the incorporation of a 5,12-epoxy ring. Compound 55 is identified as an exceptionally symmetrical diterpene dimer characterized by the formation of a cyclobutane ring through [2 + 2] cycloaddition (Table 3, Figure 4).

Table 3.

Chemical constituents of clerodane-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
29	15-nor-cleroda-3,12-diene	D. amber	-	[14]
30	callinteger A	C. integerrima	twigs and leaves	[15]
31	callinteger B	C. integerrima	twigs and leaves	[15]
32	trans-dehydrocrotonin	C. cajucara	tree	[16]
33	croyanoid B	C. yanhuii	twigs and leaves	[17]
34	crotoeurin B	C. euryphyllus	twigs and leaves	[18]
35	crocleropene B	C. caudatus	twigs and leaves	[19]
36	crocleropene A	C. caudatus	twigs and leaves	[19]
37	croyanoid C	C. yanhuii	twigs and leaves	[17]
38	tinocapillin A	T. capillipes	rhizomes	[20]
39	tinocallone A	T. capillipes	rhizomes	[20]
40	tinocallone C	T. capillipes	rhizomes	[20]
41	tinocapillin B	T. capillipes	rhizomes	[20]
42	tinocapillin C	T. capillipes	rhizomes	[20]
43	crotoeurin C	C. euryphyllus	twigs and leaves	[18]
44	6-epi-crotoeurin C	C. crassifolius	roots	[21]
45	teucvidin	C. euryphyllus	twigs and leaves	[18]
46	isoteucvin	C. euryphyllus	twigs and leaves	[18]
47	teucvin	C. euryphyllus	twigs and leaves	[17,18]
48	isocrotocaudin	C. euryphyllus	twigs and leaves	[17,18]
49	crotocaudin	C. crassifolius	roots	[21]
50	croyanoid D	C. yanhuii	twigs and leaves	[17]
51	teucvisin C	T. viscidum	whole plants	[22]
52	teucvisin D	T. viscidum	whole plants	[22]
53	teucvisin E	T. viscidum	whole plants	[22]
54	croyanoid A	C. yanhuii	twigs and leaves	[17]
55	crotoeurin A	C. euryphyllus	twigs and leaves	[17,18]

Figure 4.

Structures of clerodane-type C19 norditerpenes.

2.3. Pimarane

Pimarane norditerpenes are tricyclic diterpenes and are widely distributed in nature. Pimarane norditerpenes are mainly divided into four types (Figure 5): pimarane, isopimarane, ent-pimarane, and ent-isopimarane. Isopimarane norditerpenes are a class of compounds classified by pimarane norditerpenes according to the difference of chiral centers in the molecule, and they are also the largest number of pimarane norditerpenes (Table 4, Figure 6).

Figure 5.

Basic skeletons of pimarane-type C19 norditerpenes.

Table 4.

Chemical constituents of pimarane-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
56	fluacinoid D	F. acicularis	aerial parts	[23]
57	fluacinoid E	F. acicularis	aerial parts	[23]
58	fluacinoid F	F. acicularis	aerial parts	[23]
59	fluacinoid G	F. acicularis	aerial parts	[23]
60	fluacinoid H	F. acicularis	aerial parts	[23]
61	aquilariaene F	C. eaglewood	-	[24]
62	aquilariaene H	C. eaglewood	-	[24]
63	jbir-65	Actinomadura sp. KC 191	-	[25]
64	actinomadurol	Actinomadura sp. KC 191	-	[25]
65	icatrichanone	I. trichantha	tubers	[26]
66	14-hydroxyicatrichanone	I. trichantha	tubers	[26]
67	3-O-methylicatrichanone	I. trichantha	tubers	[26]
68	3-O-methyl-14-hydroxyicatrichanone	I. trichantha	tubers	[26]
69	7α-hydroxyicacenone	I. trichantha	tubers	[27]
70	icacenone	I. trichantha	tubers	[27]
71	12-hydroxy-icacinlactone	I. trichantha	tubers	[27]
72	icacinlactone H	I. trichantha	tubers	[27]
73	icacinlactone A	I. trichantha	tubers	[28]
74	icacinlactone B	I. trichantha	tubers	[27,28]
75	icacinlactone E	I. trichantha	tubers	[28]
76	icacinlactone F	I. trichantha	tubers	[28]
77	icacinlactone G	I. trichantha	tubers	[28]
78	icacinlactone C	I. trichantha	tubers	[28]
79	icacinlactone D	I. trichantha	tubers	[27,28]
80	trichanthol B	I. trichantha	tubers	[27]
81	8β-hydroxy-18-nor-4(5),15-isopimaradien-3-one	E. grandiflflorus Wall.	branches and leaves	[29]
82	18(4→14), 19(4→8)-bis-abeo-nor-isopimarane-1,5-diene-3-yl-3β-methoxy propyl pentanoate	P. malabarica	edible portion	[30]
83	smardaesidin F	C. purpureus	-	[31]
84	smardaesidin G	C. purpureus	-	[31]
85	sphaeropsidin G	D. olivarum	-	[32]
86	taichunin D	A. taichungensis	-	[33]
87	aspewentin D	A. wentii EN-48	-	[34]
88	aspewentin E	A. wentii EN-48	-	[34]
89	aspewentin F	A. wentii EN-48	-	[34]
90	aspewentin I	A. wentii EN-48	-	[35]
91	aspewentin J	A. wentii EN-48	-	[35]
92	aspewentin K	A. wentii EN-48	-	[35]
93	aspewentin M	A. wentii EN-48	-	[35]
94	aspewentin L	A. wentii EN-48	-	[35]
95	aspewentin C	A. wentii EN-48	-	[36]
96	aspewentin A	A. wentii EN-48	-	[36]
97	aspewentin B	A. wentii EN-48	-	[36]
98	aspewentin G	A. wentii EN-48	-	[34]
99	aspewentin H	A. wentii EN-48	-	[34]
100	xylarilongipin A	A. wentii EN-48	-	[37]
101	asperether A	A. wentii EN-48	-	[38]
102	asperether B	A. wentii EN-48	-	[38]
103	asperether C	A. wentii EN-48	-	[38]
104	asperether D	A. wentii EN-48	-	[38]
105	asperether E	A. wentii EN-48	-	[38]
106	(2S,3S,5S,9S,10S,13S)-2,3-dihydroxy-16-nor-ent-pimar-8(14)-en-15-oic acid	F. fimbriata	aerial parts	[39]
107	(3R,5S,9S,10S,13S)-2-hydroxy-16-nor-ent-pimar-8(14)-en-15-oic acid	F. fimbriata	aerial parts	[39]
108	(2S,3R,5S,9S,10S,13S)-2-acetoxy-3-hydroxy-16-nor-ent-pimar-8(14)-en-15-oic acid	F. fimbriata	aerial parts	[39]
109	norflickinflimiod A	F. fimbriata	aerial parts	[39,40]
110	(2S,3R,5S,9S,10S,13S)-2-O-E-cinnamoyl-3-hydroxy-16-nor-ent-pimar-8(14)-en-15-oic acid	F. fimbriata	aerial parts	[39]
111	3α,14β-diacetoxy-16-nor-ent-pimar-15α,8-olide	F. fimbriata	aerial parts	[39]
112	norflickinflimiod B	F. fimbriata	aerial parts	[39,40]
113	norflickinflimiod C	F. fimbriata	aerial parts	[40]
114	norflickinflimoside	F. fimbriata	aerial parts	[40]
115	norflickinflimiod D	F. fimbriata	aerial parts	[40]
116	eupneria K	E. neriifolia	stem bark	[41]
117	eupneria L	E. neriifolia	stem bark	[41]
118	eupneria J	E. neriifolia	stem bark	[41]
119	eupneria M	E. neriifolia	stem bark	[41]
120	(3R,4R,5S,9R,10S,12S,13S)-ent-18-nor-8(14),15-isopimaradiene-3β,12β,4α-triol	E. neriifolia	stems	[42]

Figure 6.

Structures of pimarane-type C19 norditerpenes.

2.3.1. Pimarane

Compounds 56–75 belong to the category of pimarane-type norditerpene compounds. Compounds 56–60 featured a methoxy group at C-12 and included a vinyl fragment at C-13. Compounds 63–64 are exceptional members within the bacterial norditerpene metabolite family. Compounds 65–77 exhibit a tetracyclic structure with a 3,20-epoxy bridge, except for compounds 69–77, which also feature lactone carbon at C-19, indicating the presence of the 19,6-gamma-lactone moiety. Compound 77 has been identified as (9βH)-17-norpimarane dilactone. Additionally, both compounds 78 and 79 exhibit β orientation of the 2,20-epoxy bridge. Compound 80 represents the first example of a glucoside derivative of 17-nor-pimarane diterpenes.

2.3.2. Isopimarane

Compounds 81–105 are isopimarane-type norditerpene compounds, with compound 82 featuring a bulky O-propyl pentanoate group at C-3. Compounds 90–95 exhibit unique examples of the 20-nor-isopimarane type, characterized by the presence of a cyclohexa-2,5-dien-1-one moiety. Compounds 96–99 represent four aromatic norditerpenes. Compound 100 possesses an unusual skeleton composed of an 18-nor-9, 16-cyclo-isopimarane framework with a cage-like bicycle [2.2.2] octane moiety. Lastly, compounds 101–105 display a rare 14,16-cyclic ether unit and possess a unique 6/6/6/5 tetracyclic cycloether skeleton.

2.3.3. Ent-Pimarane

Compounds 106–109 exhibit an ester bond instead of the olefinic bond at C-13. Compound 110 displays an additional cinnamoyl group and a vinyl benzene moiety. Compounds 111–115 are characterized by a rare 16-nor-ent-pimarane skeleton and demonstrate the presence of γ-lactone between the C₁₅-O-C₈ bonds. Compound 115 represents the first reported instance of this previously undescribed skeleton of 2, 3-seco-16-nor-ent-pimarane.

2.3.4. Ent-Isopimarane

Compounds 116–117 represent the first examples of 18 (or 19)-ent-isopimarane norditerpenes. Compound 117 has a double bond at C-14, while compounds 118–120 feature a hydroxyl group at C-4, with compound 119 being the C-4 epimer of 120.

2.4. Abietane

Abietane norditerpenes are tricyclic diterpenes commonly formed through rearrangements of pimarane norditerpenes. The core structure consists of a hydrogenated phenanthrene with an isopropyl group at C-13, geminal dimethyl groups at C-4, and a methyl group at C-20. Ring B and the side chains on the C ring can easily undergo rearrangement to form a five-membered ring, with some quinone structures also found on the C ring. Abietane norditerpenes are primarily classified into abietane type, ent-abietane type, and seco-abietane type (in Table 5, Figure 7).

Table 5.

Chemical constituents of abietane-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
121	dichroanone	S. deserta	roots	[43]
122	salviadesertin A	S. deserta	roots	[43]
123	salviadesertin B	S. deserta	roots	[43]
124	salviadesertin E	S. deserta	roots	[43]
125	salviadesertin F	S. deserta	roots	[43]
126	dehydromiltirone	S. miltiorrhiza	cell	[44]
127	grandifolia D	S. grandifolia	roots	[45]
128	2-isopropyl-8,8-dimethyl-7,8-dihydroph-enanthrene-1,4,5(6H)-trione	S. leriifolia	whole plants	[46]
129	deoxyneocryptotanshinone	S. rhytidea	roots	[47]
130	(1R,15R)-1β-hydroxyneocryptotanshinone.	P. abrotanoides	roots	[48]
131	19-nor-abieta-4,6,8,11,13-tetraen-3-one	P. euphratica	resins	[49]
132	4,4α,9,10-tetrahydro-1,4α-dimethyl-7-isopropyl-2(3H)-phenanthrone	P. euphratica	resins	[49]
133	19-nor-abieta-4(18),8,11,13-tetraen-7-one	P. euphratica	resins	[49]
134	castanol B	S. castanea	whole plants	[50]
135	triptobenzene S	T. wilfordii	roots	[51]
136	1-deoxo aurocadiol	S. rhytidea	roots	[47]
137	arucadiol	S. rhytidea	roots	[47]
138	1-deoxy-1,2-dien-3-oxoarucadiol.	P. abrotanoides	roots	[48]
139	euphorane C	E. dracunculoides	powder	[52]
140	nagiol A	P. nagi	leaves	[53]
141	18-norabieta-8,11,13-4-ol	P. euphratica	resins	[49]
142	grandifolia A	S. grandifolia	roots	[45]
143	isograndifoliol	P. atriplicifolia	roots	[45,54]
144	grandifolia B	S. grandifolia	roots	[45]
145	przewalskin Y-1	P. abrotanoides	roots	[48]
146	miltipolone	S. grandifolia	roots	[45]
147	dehydrodanshenol A	S. przewalskii	roots	[55]
148	cryptotanshinone	S. miltiorrhiza	seeds	[44,56]
149	tanshinone IIA	S. miltiorrhiza	seeds	[56]
150	methyltanshinoate	S. castanea	whole plants	[50]
151	1-oxocryptotanshinone	P. atriplicifolia	roots	[48]
152	(1R,15R)-1-acetoxycryptotanshinone	P. atriplicifolia	roots	[54]
153	(1R)-1-acetoxytanshinone IIA	P. atriplicifolia	roots	[54]
154	(15R)-1-oxoaegyptinone A	P. atriplicifolia	roots	[54]
155	rubesanolide F	I. rubescens	leaves	[57]
156	rubesanolide G	I. rubescens	leaves	[57]
157	castanol A	S. castanea	whole plants	[50]
158	abieseconordine A	A. forrestii	twigs	[58]
159	abieseconordine B	A. forrestii	twigs	[58]
160	5-(6-isopropyl-2-methylnaphthalen-1-yl)pentan-2-one	P. euphratica	resins	[49]
161	deacetylsalvianonol	S. przewalskii	roots	[55]
162	sessilifol O	C. sessilifolius	whole plants	[59]
163	salvialba acid	S. miltiorrhiza	roots	[60]
164	salprzelactone	S. przewalskii	roots	[55]

Figure 7.

Structures of abietane-type C19 norditerpenes.

Compounds 121–123 belong to the 8-nor-7(8→14),9(8→7)-di-abeo-abietane skeleton type. Compounds 124–125 possess a 6-nor-6,7-seco-abietane skeleton. Compounds 126–127 contain a moiety of 1,2-quinone, while compounds 128–130 feature a moiety of 1,4-quinone in ring C. Compounds 126–141 are aromatic norditerpenes, while compounds 142–146 feature a tropolone moiety; notably, compound 142 is characterized by the presence of a peroxide group connecting C-8 and C-12. Furthermore, compounds 147–153 demonstrate rearranged side chains that form an oxygen-containing five-membered ring. Compounds 155–156 possess a unique γ-lactone subgroup located between C-8 and C-20. Compound 157 is a seven-membered norditerpene featuring two carbonyl groups in the C ring. Compounds 158–162 are seco-abietane norditerpenes. Compounds 158–159 possess a unique 18-nor-5,10: 9,10-disecoabietane skeleton, while compound 160 exhibits a rearranged angular methyl group at C-5 and belongs to the 4, 5-seco-19-nor-abietane skeleton. Compound 163 is characterized by a 7β,19-epoxydecalin spirally linked with a five-membered α, β-unsaturated lactone ring, and an acrylic acid moiety.

2.5. Kaurane

Kaurane norditerpenes represent a class of tetracyclic diterpenes characterized by the hydrophenanthrene core skeleton. These compounds can be classified into two configurations, namely kaurane and ent-kaurane. It is worth noting that the ent-kaurane-type norditerpenes exhibit remarkable abundance (Table 6, Figure 8).

Table 6.

Chemical constituents of kaurane-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
165	laxiflorolide M	I. eriocalyx	leaves	[61]
166	ternifolide B	I. ternifolius	-	[62]
167	ent-16-oxo-17-nor-kauran-19-oic	B. retusa	aerial parts	[63]
168	sideritone A	S. pullulans	aerial parts and roots	[64]
169	sideritone B	S. pullulans	aerial parts and roots	[64]
170	amentotaxin L	A. argotaenia	twigs and leaves	[65]
171	18-nor-ent-kaur-4(19)-en-17-oic acid	M. senegalensis	root bark	[66]
172	16α,17,19-trihydroxy-18-nor-ent-kauran-4β-ol	W. trilobata	whole plants	[67]
173	amentotaxin M	A. argotaenia	twigs and leaves	[65]
174	amentotaxin C	A. argotaenia	twigs and leaves	[65]
175	amentotaxin D	A. argotaenia	twigs and leaves	[65]
176	amentotaxin E	A. argotaenia	twigs and leaves	[65]
177	amentotaxin F	A. argotaenia	twigs and leaves	[65]
178	amentotaxin G	A. argotaenia	twigs and leaves	[65]
179	amentotaxin H	A. argotaenia	twigs and leaves	[65]
180	amentotaxin I	A. argotaenia	twigs and leaves	[65]
181	amentotaxin J	A. argotaenia	twigs and leaves	[65]
182	amentotaxin K	A. argotaenia	twigs and leaves	[65]
183	19-nor-16,17-dihydroxy-ent-kaur-4(18)-ene	C. haumanianus	leaves and stem bark	[68]
184	wilkaunoid D	T. wilfordii	stems	[69]
185	(4α)-19-nor-ent-kaurane-4,16,17-triol	A. squamosa L.	stem bark	[70]
186	(4α,16α)-17-(acetyloxy)-19-nor-ent-kaurane-4,16-diol	A. squamosa L.	stem bark	[70]
187	phyllostachysin N	I. phyllostachys	aerial parts	[71]
188	phyllostachysin O	I. phyllostachys	aerial parts	[71]
189	isorosthin A	I. rosthornii	aerial parts	[72]

Figure 8.

Structures of kaurane-type C19 norditerpenes.

Compounds 165–166 are spiral seco ent-kaurane norditerpenes. Compound 165 is a naturally occurring compound with a structure of 6-nor-6,7-seco-ent-kauranoid, while compound 166 featured a 6,7: 8,15-seco-ent-kaurane diterpene skeleton.

Compounds 170–182 are classified as ent-18-norkaurene-type diterpenes. Compound 173 features an 11β,16β-epoxy ring moiety. Compounds 174–182 exhibit a 4β, 19-epoxy ring moiety. Compounds 183–186 are categorized as C-19 nor-ent-kaurane norditerpenes.

Compounds 187–188 demonstrate a unique structural pattern of 20-nor-ent-kaurane norditerpenes. Compound 189 is determined to be a nor-6,7-seco-1,7: 6, 11-diolide-ent-kaurane, and the first diterpenene within the category of the 20-nor-enmein type.

2.6. Cephalotane

In the past decade, more than fifty cephalotane-type norditerpenes have been discovered through previous phytochemical investigations, which can be categorized into four distinct structural groups: A-ring-contracted cephalotane-type norditerpenes, cephalotaxus troponoids (C19), 17-nor-cephalotane-type diterpenes (C19), and cephalotane dimers (Table 7, Figure 9).

Table 7.

Chemical constituents of cephalotane-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
190	cephalotanin A	C. sinensis	leaves	[73]
191	cephalotanin B	C. sinensis	leaves	[73]
192	cephalotanin C	C. sinensis	leaves	[73]
193	ceforalide F	C. fortunei	seeds	[74]
194	ceforalide G	C. fortunei	seeds	[74]
195	ceforalide H	C. fortunei	seeds	[74]
196	cephalotanin D	C. sinensis	leaves	[73]
197	cephanolide D	C. sinensis	twigs and leaves	[75]
198	ceforalide A	C. fortunei	seeds	[74]
199	ceforalide B	C. fortunei	seeds	[74]
200	ceforalide C	C. fortunei	seeds	[74]
201	ceforalide D	C. fortunei	seeds	[74]
202	ceforalide E	C. fortunei	seeds	[74]
203	fortalpinoid P	C. fortunei	seeds	[76]
204	fortalpinoid Q	C. fortunei	seeds	[76]
205	20-oxohainanolidol	C. fortunei	twigs and leaves	[77]
206	20α-hydroxyhainanolidol	C. fortunei	twigs and leaves	[77]
207	10-hydroxyhainanolidol	C. fortunei	twigs and leaves	[77]
208	cephinoid H	C. fortunei	twigs and leaves	[78]
209	cephinoid I	C. fortunei	twigs and leaves	[78]
210	cephinoid J	C. fortunei	twigs and leaves	[78]
211	cephinoid K	C. fortunei	twigs and leaves	[78]
212	cephinoid L	C. fortunei	twigs and leaves	[78]
213	cephinoid M	C. fortunei	twigs and leaves	[78]
214	hainanolidol	C. fortunei	twigs and leaves	[78]
215	fortunolide A	C. fortunei	twigs and leaves	[78]
216	fortalpinoid A	C. fortunei	seeds	[76]
217	fortalpinoid B	C. fortunei	seeds	[76]
218	fortalpinoid C	C. fortunei	seeds	[76]
219	fortalpinoid D	C. fortunei	seeds	[76]
220	fortalpinoid E	C. fortunei	seeds	[76]
221	fortalpinoid F	C. fortunei	seeds	[76]
222	3-deoxyfortalpinoid F	C. fortunei	seeds	[76]
223	10-hydroxyharringtonolide	C. mannii	twigs and leaves	[78,79]
224	cephinoid F	C. fortunei	twigs and leaves	[78]
225	cephinoid G	C. fortunei	twigs and leaves	[78]
226	harringtonolide	C. fortunei	twigs and leaves	[78]
227	fortunolide B	C. fortunei	twigs and leaves	[78]
228	fortalpinoid J	C. fortunei	seeds	[76]
229	6-en-harringtonolide	C. mannii	twigs and leaves	[78,79]
230	fortalpinoid H	C. fortunei	seeds	[76]
231	fortalpinoid I	C. fortunei	seeds	[76]
232	cephanolide J	C. fortunei	seeds	[76]
233	fortalpinoid G	C. fortunei	seeds	[76]
234	cephinoid N	C. fortunei	twigs and leaves	[78]
235	cephinoid O	C. fortunei	twigs and leaves	[78]
236	fortalpinoid M	C. fortunei	seeds	[76]
237	fortalpinoid N	C. fortunei	seeds	[76]
238	fortalpinoid O	C. fortunei	seeds	[76]
239	cephafortoid A	C. fortunei	twigs and leaves	[77]
240	14-epi-cephafortoid A	C. fortunei	twigs and leaves	[77]
241	cephinoid P	C. fortunei	twigs and leaves	[78]
242	cephinoid Q	C. fortunei	twigs and leaves	[78]
243	cephinoid R	C. fortunei	twigs and leaves	[78]
244	cephinoid S	C. fortunei	twigs and leaves	[78]
245	gongshanolide	C. fortunei	twigs and leaves	[78]
246	fortalpinoid K	C. fortunei	seeds	[76]
247	fortalpinoid L	C. fortunei	seeds	[76]
248	ceforalide I	C. fortunei	seeds	[74]
249	cephalodione A	C. fortunei	seeds	[80]
250	cephalodione B	C. fortunei	seeds	[80]
251	cephalodione C	C. fortunei	seeds	[80]
252	cephalodione D	C. fortunei	seeds	[80]

Figure 9.

Structures of cephalotane-type C19 norditerpenes.

Compounds 190–202 are norditerpenes featuring a contracted A-ring structure. Compound 192 exhibits a distinctive bicyclo [4.1.0] hepta-2,4-dien-7-one moiety. Compounds 203–235 belong to cephalotaxus troponoids, which represent the predominant group of cephalotane-type norditerpenes. The skeletal structure of cephalotaxus troponoids is distinguished by a highly rigid tetracyclic carbon framework, encompassing a tropone moiety, multiple oxygenated groups, and methyl substituents at positions C-4 and C-12. Cephalotaxus troponoids are derived from labdane-type norditerpenes. The 17-nor-cephalotane-type diterpenes were derived from cephalotaxus troponoids via a reduction in the tropone ring. Compounds 236–248 exemplify this class of diterpenes, while compound 247 features an 8-oxabicyclo [3.2.1] oct-2-ene moiety. Compounds 249–252 represent the first example of C19 norditerpene dimers and possess a unique tricycle [6.4.1.1^{2, 7}] tetradeca-3,5,9,11-tetraene-13,14-dione core, and both ends are terminated with a C₂ symmetric or asymmetric rigid polycyclic ring system.

2.7. Cembranoid

Cembranoid-type norditerpenes are macrocyclic diterpenes that belong to a class of natural products characterized by fourteen-membered rings and possess three symmetrically distributed methyl groups and one isopropyl group. Isopropyl-cembrane-type norditerpenes, primarily formed through isopropyl or isopropenyl substitution, represent the most common cembrane-type norditerpenes (Table 8, Figure 10).

Table 8.

Chemical constituents of cembranoid-type C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
253	xiguscabrolide H	S. scabra	-	[81]
254	10-epi-gyrosanolide E	S. scabra	-	[81]
255	5-epi-sinuleptolide	S. scabra	-	[81]
256	norcembrene 5	S. scabra	-	[81]
257	scabrolide D	S. scabra	-	[81]
258	scabrolide G	S. scabra	-	[81]
259	sinularcasbane O	S. scabra	-	[81]
260	gyrosanolide F	S. scabra	-	[81]
261	sinuleptolide	S. scabra	-	[81]
262	5-epi-norcembrene	S. maxima	-	[82]
263	13-epi-scabrolide C	S. maxima	-	[82]
264	sinudenoid A	S. densa	-	[83]
265	sinudenoid B	S. densa	-	[83]
266	sinudenoid C	S. densa	-	[83]
267	sinudenoid D	S. densa	-	[83]
268	ineleganolide	S. maxima	-	[81,82,84,85]
269	fragilolide A	J. fragilis	-	[86]
270	sinuscalide C	S. scabra	-	[87]
271	sinuscalide D	S. scabra	-	[87]
272	sinuscalide B	S. scabra	-	[87]
273	scabrolide B	S. densa	-	[83]
274	scabrolide A	S. densa	-	[83]
275	sinudenoid E	S. densa	-	[83]
276	sinuscalide A	S. scabra	-	[87]

Figure 10.

Structures of cembranoid-type C19 norditerpenes.

Compounds 253–263 are characterized by the presence of polycyclic furanobutenolide-derived norcembranoid diterpenes isolated from soft corals. Compound 264 possesses a rare 5/5/11-fused tricyclic ring system, while compounds 265–267 possess a 5/5/6/6 tetracyclic ring system. Compounds 268–274 possess a cyclopentane ring, a cyclohexane ring, and a seven-membered ring. Compounds 275–276 display an uncommon 8/8 bicyclic carbon core.

2.8. Others

Compounds 277–278 are lathyrane-type norditerpenes. Compound 279 is an atypical C19 furano-norditerpene. Compounds 280–282 have uncommon characteristics as cassane-type norditerpenes. The classification of compounds 283–286 confirms their identity as cleistanthane-type norditerpenes. The discovery of compounds 283–284 marks the first examples of phenylethylene-bearing derivatives among 20-nor-diterpenes, with compound 284 exhibiting a unique 3,10-oxybridge moiety. Compound 286 stands out due to its scarcity among phenylacetylene-containing 18-nor-diterpene glycosides. Compounds 287–291 exhibit the characteristic fusicoccane-type norditerpenes. Specifically, compounds 287–289 belong to a unique category of 16-nor-dicyclopenta [a,d]-cyclooctane norditerpenes, while compound 287 features an undescribed tetracyclic ring system with a configuration of 5/6/6/5. Compounds 292–293 are obtained through the rearrangement of the crotofolane skeleton. Compounds 294–295 exhibit a pair of enantiomeric norditerpenes featuring an unexpected 6/5/6/6-fused tetracyclic ring system. Compounds 296–298 are uniformly classified as ent-atisane norditerpenes. Compound 299 possesses a perhydroazulene ring system, while compounds 300–302 represent three newly rearranged oxygenated terpenes. Compounds 303–304 belong to the class of spongian diterpenes and exhibit a highly distinctive carbon skeleton known as 3-nor-spongian. Li’s group unveiled four unprecedented C19 norditerpenes, including compound 305 with a cyclopenta[b]furan-2,5-dione skeleton, compound 306 with a pyran[b]furan-2,6-dione skeleton, and compounds 307–308, which are epimerides possessing a pair of dioxaspiro[4.4]nonane skeletons.

Compound 309 is a naturally occurring norditerpene with a seven-membered ring mulinane skeleton lacking the C-16-methyl group. Compound 310 possesses an undescribed nor-guanacastane skeleton. Compound 312 has been identified as an isomer of 311. Compounds 313–314 belong to yonarane norditerpenes, and compound 317 belongs to inelegane-type norditerpenes. Compound 315 is considered an undescribed bicyclo[11.3.0]hexadecane carbon skeleton, whereas compounds 316–321 are consistently classified as verticillane-type norditerpenes. Compounds 322–323 are norditerpene glycosides. Compounds 324–332 represent new norditerpene lactones, whereas compounds 333–345 are norditerpene oidiolactones. Compounds 347–358 have been identified as norditerpene picrotoxanes. Compound 359 exhibits a podocarpane skeleton, while compound 360 belongs to the xeniaphyllane-type norditerpene. Compounds 363–364 are a heterodimeric diterpene consisting of an ent-abietane and an 18-nor-rosane skeleton with an aromatic ring (Table 9, Figure 11).

Table 9.

Chemical constituents of other compounds of C19 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
277	japodagricanone A	J. podagrica	twigs and leaves	[88]
278	japodagricanone B	J. podagrica	twigs and leaves	[88]
279	6-((E)-12-(furan-13-yl)-10-methylpent-10-en-9-yl)-6,7,8,8atetrahydro-3H-isochromen-1-(5H)-one	U. (Photololigo) duvaucelii	-	[89]
280	erythro-norcassanoid A	E. fordii	roots	[90]
281	erythro-norcassanoid B	E. fordii	roots	[90]
282	caesalpinone	C. decapetala var. japonica	roots	[91]
283	aspidoptoid A	A. obcordata	vine	[92]
284	aspidoptoid B	A. obcordata	vine	[92]
285	phyllanflexoid C	P. flexuosus	roots	[93]
286	olicleistanone	D. olivarum	-	[32]
287	alterbrassicicene B	A. brassicicola	-	[94]
288	1β-hydroxy-brassicicene Q	A. brassicicola	-	[94]
289	3-ketobrassicicene W	A. brassicicola	-	[94]
290	aculeaterpene A	A. aculeatinus	-	[95]
291	dongtingnoid C	P. sp. DT10	-	[96]
292	crotocascarin α	C. cascarilloides	stems	[97]
293	crotocascarin β	C. cascarilloides	stems	[97]
294	(+)-paeoveitol	P. veitchii	roots	[98]
295	(−)-paeoveitol	P. veitchii	roots	[98]
296	eurifoloid M	E. neriifolia	twigs and leaves	[99]
297	eurifoloid P	E. neriifolia	twigs and leaves	[99]
298	adipoiloside	A. poilanei	leaves	[100]
299	citrinovirin	T. citrinoviride	-	[101]
300	16-deacetoxy-9,11-dihydrogracilin A	G. Mollusks	-	[102]
301	15,16-deacetoxy-15-hydroxy-9,11-dihydrogracilin A	G. Mollusks	-	[102]
302	verrielactone	G. Mollusks	-	[102]
303	3-nor-spongiolide A	S. officinalis	-	[103]
304	3-nor-spongiolide B	S. officinalis	-	[103]
305	scrodentoid F	S. dentata	whole plants	[104]
306	scrodentoid G	S. dentata	whole plants	[104]
307	scrodentoid H	S. dentata	whole plants	[104,105]
308	scrodentoid I	S. dentata	whole plants	[104,105]
309	normulin-11-en-13-oxo-20-oic acid	A. compacta	aerial part	[106]
310	pyromyxone D	C. pyromyxa	fruiting bodies	[107]
311	adenica	L. zeylanica	whole plants	[108]
312	6β-acetoxy-9α,13-epoxy-16-norlabd-13E-en-15-al	L. zeylanica	whole plants	[108]
313	scabrolide A	S. scabra	-	[81]
314	yonarolide	S. scabra	-	[81]
315	12-hydroxy-scabrolide A	S. scabra	-	[81]
316	sinusiaetone A	S. siaesensis	-	[109]
317	cespitaenin A	C. taeniata	-	[110]
318	cespitaenin B	C. taeniata	-	[110]
319	cespitulin Q	Cespitularia sp.	-	[111]
320	cespitulin R	Cespitularia sp.	-	[111]
321	cespitulin P	Cespitularia sp.	-	[111]
322	norhawthornoid A	C. pinnatifida	leaves	[112]
323	norhawthornoid B	C. pinnatifida	leaves	[112]
324	ebractenoid A	E. ebracteolata	roots	[113]
325	ebractenoid B	E. ebracteolata	roots	[113]
326	(2S,7S,11S)-(8E,12Z)-2, 10-dihydroxy-pellialactone	A. chinense	roots	[114]
327	(2S,4S,7S,11S)-(8E,12Z)-2,4,10-trihydroxy-pellialactone	A. chinense	roots	[114]
328	miltiolactone A	S. miltiorrhiza	roots	[115]
329	miltiolactone B	S. miltiorrhiza	roots	[115]
330	taichunin A	A. taichungensis	-	[33]
331	taichunin B	A. taichungensis	-	[33]
332	taichunin C	A. taichungensis	-	[33]
333	PR 1388	O. truncatum	-	[116]
334	oidiolactone D	O. truncatum	-	[116]
335	oidiolactone C	O. truncatum	-	[116]
336	oidiolactone G	O. truncatum	-	[116]
337	epi-oidiolactone G	O. truncatum	-	[116]
338	oidiolactone H	O. truncatum	-	[116]
339	oidiolactone I	O. truncatum	-	[116]
340	oidiodendronic acid	O. truncatum	-	[116]
341	oidiolactone E	O. truncatum	-	[116]
342	LL-Z1271α	O. truncatum	-	[116]
343	oidiolactone J	O. truncatum	-	[116]
344	oidiolactone K	O. truncatum	-	[116]
345	oidiolactone L	O. truncatum	-	[116]
346	LL-Z1271β	O. truncatum	-	[116]
347	16-epi-pretoxin	A. carunculatus	fruits	[117]
348	austrobuxusin F	A. carunculatus	fruits	[117]
349	austrobuxusin G	A. carunculatus	fruits	[117]
350	austrobuxusin H	A. carunculatus	fruits	[117]
351	16-epi-austrobuxusin H	A. carunculatus	fruits	[117]
352	16-epi-austrobuxusin G	A. carunculatus	fruits	[117]
353	austrobuxusin I	A. carunculatus	fruits	[117]
354	austrobuxusin J	A. carunculatus	fruits	[117]
355	16-epi-austrobuxusin B	A. carunculatus	fruits	[117]
356	austrobuxusin K	A. carunculatus	fruits	[117]
357	austrobuxusin L	A. carunculatus	fruits	[117]
358	austrobuxusin M	A. carunculatus	fruits	[117]
359	methyl-13-acetyl-podocarpa-8,11,13-trien-18-oate	P. euphratica	resins	[49]
360	sinuhirtone B	S. hirta	-	[118]
361	9,11-dihydrogracilin A	D. antarctica	-	[119]
362	9,11-dihydrogracillinone A	D. antarctica	-	[119]
363	eupractenoid A	E. ebracteolata	roots	[120]
364	eupractenoid B	E. ebracteolata	roots	[120]

Figure 11.

Structures of other compounds of C19 norditerpenes.

3. Chemical Constituents of C18 Norditerpenes

Ten primary categories of C18 norditerpenes have been identified in the natural environment, including the labdane, abietane, podocarpane, pimarane, cassane, aspergilane, benzodioxane, commiphorane, totarane, and cephalotane types. Additionally, there are other norditerpenes with atypical structures and certain abietane dipolymers found in nature (Table 10, Figure 12).

Table 10.

Chemical constituents of C18 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
365	salyunnanin F	S. yunnanensis	roots	[121]
366	16,17-dinorpisferal A	S. digitaloides	roots	[122]
367	militibetin A	S. miltiorrhiza	dry roots	[48]
368	(5S,8S,10R)-militibetinA	P. abrotanoides	roots	[48]
369	normiltioane	S. miltiorrhiza	cell cultures	[44]
370	yunnannin A	S. miltiorrhiza	dry roots	[123]
371	(5S,6S,7R,10R)-16,17-bis-nor-7α-hydroxy-18,6-epoxyferruginol	P. abrotanoides	roots	[48]
372	(5S,6S,7S)-16,17-bis-nor-7α-hydroxyferruginol-18,6-olide	P. abrotanoides	roots	[48]
373	przewalskin	S. digitaloides	roots	[122]
374	(5S,6S,7R,10R)-16,17-bis-nor-6β-hydroxy-18,7-epoxyferruginol	P. abrotanoides	roots	[48]
375	(5R,7S,10R)-3-oxoprzewalskin	P. abrotanoides	roots	[48]
376	grandifolia C	P. abrotanoides	roots	[48]
377	2-isopropyl-8-methylphenan-threne-3,4-dione	S. miltiorrhiza	cell cultures	[44]
378	(5S,10R)-16,17-bis-nor-pisiferanol	P. abrotanoides	roots	[48]
379	5S-1,2-dihydroheudelotinol	T. chinensis	stem bark and wood	[124]
380	deoxofaveline	P. abrotanoides	roots	[48]
381	trigonostemon A	T. chinensis	stem bark and wood	[124]
382	trigonostemon B	T. chinensis	stem bark and wood	[124]
383	5S-heudelotinone	T. chinensis	stem bark and wood	[124]
384	trigonostemon C	T. chinensis	stem bark and wood	[124]
385	trigonostemon D	T. chinensis	stem bark and wood	[124]
386	heudelotinone	T. howii	stems and leaves	[124]
387	norperovskatone	P. atriplicifolia	flowers	[125]
388	salviolone	P. abrotanoides	roots	[48]
389	epi-castanolide	P. abrotanoides	roots	[48]
390	cryptoacetalide	S. miltiorrhiza	cell cultures	[44]
391	epicryptoacetalide	S. miltiorrhiza	cell cultures	[44]
392	epi-danshenspiroketallactone A	S. miltiorrhiza	cell cultures	[44]
393	tanshinone I	S. digitaloides	cell cultures	[56,122]
394	dihydrotanshinone I	S. miltiorrhiza	cell cultures	[56]
395	dihydrotanshinone	S. digitaloides	roots	[122]
396	dihydroisotanshinone I	S. miltiorrhiza	cell cultures	[44]
397	tanshinketolactone	S. miltiorrhiza	cell cultures	[44]
398	trigonostemon G	T. chinensis	stem bark	[126]
399	trigonostemon H	T. chinensis	stem bark	[126]
400	flueggenoid E	S. miltiorrhiza	roots and rhizomes	[127]
401	12-hydroxy-20(10→5)-abeo-4,5-seco-podocarpa-5(10),6,8,11,13-pentaen-3-one	S. miltiorrhiza	roots and rhizomes	[127]
402	3β,12-dihydroxy-13-methylpodocarpa-6,8,11,13-tetraene	S. digitaloides	roots	[128]
403	3α-hydroxy-12-methoxy-13-methyl-ent-podocar-6,8,11,13-tetraene	S. digitaloides	roots	[128]
404	12-hydroxy-13-methyl-ent-podocarp-6,8,11,13-tetraen-3-one	S. digitaloides	roots	[128]
405	12-methoxy-13-methyl-ent-podocarp-6,8,11,13-tetraen-3-one	S. digitaloides	roots	[128]
406	jatromulone A	T. chinensis	stem bark and wood	[129]
407	gossweilone	T. chinensis	stem bark and wood	[129]
408	flueggenoid C	S. miltiorrhiza	roots and rhizomes	[127]
409	3β,12-dihydroxy-13-methylpodocarpane-8,10,13-triene	T. chinensis	stem bark and wood	[129]
410	3β,12-dihydroxy-13-methylpodocarpa-8,11,13-triene	S. digitaloides	roots	[128]
411	3α-hydroxy-12-methoxy-13-methyl-ent-podocarpa-6,8,11,13-tetraene	S. miltiorrhiza	roots and rhizomes	[127]
412	3α,12-dihydroxy-13-methyl-ent-podocarpa-6,8,11,13-tetraene	S. miltiorrhiza	roots and rhizomes	[127]
413	6β,12-dihydroxy-13-methyl-ent-podocarp-8,11,13-trien-3-one	S. digitaloides	roots	[128]
414	rel-(5β,8α,10α)-8-hydroxy-13-methylpodocarpa-9(11),13-diene-3,12-dione	A. moluccanus	twigs	[130]
415	3α-hydroxy-13-hydroxymethyl-12-methoxy-ent-podocarp-6,8,11,13-tetraene	S. digitaloides	roots	[128]
416	3β-hydroxy-13-hydroxymethyl-12-methoxy-ent-podocarp-6,8,11,13-tetraene	S. digitaloides	roots	[128]
417	10α,12-dihydroxy-13-methyl-9(10→20)-abeo-ent-podocarpa-6,8,11,13-tetraen-3-one	S. miltiorrhiza	roots and rhizomes	[127]
418	flueggenoid A	S. miltiorrhiza	roots and rhizomes	[127]
419	flueggenoid.B	S. miltiorrhiza	roots and rhizomes	[127]
420	flueggenoid D	S. miltiorrhiza	roots and rhizomes	[127]
421	6,12-dihydroxy-13-methyl-7-oxo-ent-podocarpa-5,8,11,13-tetraeno-20,3α-lactone	S. miltiorrhiza	roots and rhizomes	[127]
422	3α,20-epoxy-3β-hydroxy-12-methoxy-13-methyl-ent-podocarp-8,11,13-triene	S. digitaloides	roots	[128]
423	7α,20-epoxy-3α-hydroxy-12-methoxy-13-methyl-ent-podocarp-8,11,13-triene	S. digitaloides	roots	[128]
424	3β-hydroxymakilactone A	P. macrophyllus	roots	[131]
425	2β-hydroxymakilactone A	P. macrophyllus	roots	[131]
426	inumakilactone A	P. macrophyllus	roots	[131]
427	makilactone M	P. macrophyllus	roots	[131]
428	inumakilactone B	P. macrophyllus	roots	[131]
429	(4S,5R,9S,10R)-methyl-19-hydroxy-15,16-dinorlabda-8(17),11E-dien-13-oxo-18-oate	A. macrophylla	-	[6]
430	pseudosinin C	P. sinensis	needles and twigs	[132]
431	pseudosinin B	P. sinensis	needles and twigs	[132]
432	8α-hydroxy-11(E)-en-13-oxo-14,15-dinorlabdan-18-oic	S. mirzayanii	-	[133]
433	austroinulin	S. rebaudiana	aerial parts	[134]
434	sterebin A	S. rebaudiana	aerial parts	[134]
435	sterebin D	S. rebaudiana	aerial parts	[134]
436	hedychin A	H. forrestii	rhizomes	[12]
437	hedychin F	H. forrestii	rhizomes	[12]
438	lyonivaloside I	L. ovalifolia	twigs and leaves	[135]
439	dryperrein A	D. perreticulata	twigs and leaves	[136]
440	dryperrein B	D. perreticulata	twigs and leaves	[136]
441	dryperrein C	D. perreticulata	twigs and leaves	[136]
442	dryperrein D	D. perreticulata	twigs and leaves	[136]
443	(2S,3R,5S,10R)-2,3-dihydroxy-15,16-dinor-ent-pimar-8,11,13-triene	F. fimbriata	aerial parts	[39]
444	(2S,3R,5S,10R)-2-acetoxy-3-hydroxy-15,16-dinor-ent-pimar-8,11,13-triene	F. fimbriata	aerial parts	[39]
445	flickinflimilin B	F. fimbriata	leaves	[137]
446	flickinflimilin A	F. fimbriata	leaves	[137]
447	norflickinflimiod E	F. fimbriata	stems	[40]
448	norflickinflimiod F	F. fimbriata	stems	[40]
449	4β-carbometoxy-14-methyltotarol	E. suaveolens	stems	[138]
450	aspergiloid I	Aspergillus sp.	culture broth	[139]
451	aleuritin	A. moluccanus	twigs	[130]
452	salviprolin A	S. przewalskii	roots	[140]
453	salviprolin B	S. przewalskii	roots	[140]
454	commiphorane A	R. Commiphora	-	[141]
455	commiphorane B	R. Commiphora	-	[141]
456	commiphoranoid C	R. Commiphora	-	[142]
457	commiphorane K	R. Commiphora	-	[143]
458	7β-hydroxynagilactone D	P. nagi	seeds	[144]
459	3-epi-15-hydroxynagilactoneD	P. nagi	seeds	[144]
460	nagilactone K	P. nagi	seeds	[144]
461	nagilactone L	P. nagi	seeds	[144]
462	3β-hydroxynagilactone L	P. nagi	seeds	[144]
463	2β-hydroxynagilactone L	P. nagi	seeds	[144]
464	1α-chloro-2β,3β,15-trihydroxynagilactone	P. nagi	seeds	[144]
465	15-hydroxynagilactone L	P. nagi	seeds	[144]
466	cephanolide A	C. sinensis	-	[75,145]
467	cephanolide B	C. sinensis	-	[75,145]
468	cephanolide C	C. sinensis	-	[75,145]
469	sinuhirtone A	S. hirta	-	[118]

Figure 12.

Structures of C18 norditerpenes.

3.1. Abietane

Compound 365 is a new abietane type and has been reported as a 20-acetyl derivative of 15,16-dinorpymara-8,11,13-trien-12-ol, known as salyunnanin F. Compound 368 is a diastereomer of 367. Compounds 370–375 exhibit an ether bridge between C-18 and C-6 or C-7. Compounds 378–388 are dinorditerpenes derived from an abietane-type skeleton with a seven-membered ring in the tricyclic skeleton. Compound 387 is a unique C18 norditerpene bearing a special seco-ring C. Compounds 389–397 belong to a special class of tetracyclic abietane-type dinorditerpenes. The stem bark of Trigonostemon chinensis yielded two novel dimeric degraded diterpenes, compounds 398–399, featuring a homodimeric biaryl skeleton derived from the rearrangement of chiral nonracemic abietane-type norditerpenes. This structural motif is connected through an axially chiral biaryl 11,11′-linkage.

3.2. Podocarpane

The podocarpane type is a trinucleated norditerpene. Compounds 400–414 and 420–423 are new 13-methyl-ent-podocarpane norditetrpenoids, while 427–428 are 12-methyl-ent-podocarpane norditetrpenoids.

Compounds 400–401 exhibit a unique dinorditerpene bearing a special seco-ring A, and 400 is a 13-methyl-3,4-seco-ent-podocarpane norditetrpenoid. Compounds 417–419 are classified as 13-methyl-9(10→20)-abeo-ent-podocarpane norditetrpenoids. Compounds 420–431 are 13-methyl-7-oxo-ent-podocarpane norditetrpenoids, and compound 420 is a derivative methylated at position 12 of compound 421. Compounds 424–428 belong to a special class of tetracyclic diterpenes.

3.3. Other Compounds

Compound 429 is an oxidized derivative of the common C20 labdane precursor and is identified as a 15,16-dinor labdane diterpene. Compounds 430–435 are determined to be 14,15-bisnor labdane diterpenes. Compounds 436–437 present the 6,7-dinorlabdane diterpenes with a peroxide bridge. Compound 438 is a special norditerpene glucoside and is defined as lyonivaloside I.

Compounds 439–448 contain a unique skeleton of 15,16-dinor-ent-pimarane diterpenes. Compound 449 represents a novel phenolic cassane norditerpene. Compound 450 exhibits a new aspergilane skeleton in structure with a special 6/5/6 tricyclic system containing an α,β-unsaturated spironolactone moiety in the B ring. Compound 451 is a novel natural product with a rare 6/6/5-fused tricyclic ring system. Compounds 452–453 are two compounds consisting of dinorditerpene and 90-norrosmarinic acid derivatives and are linked by a 1,4-benzodioxanyl motif. Compounds 454–455 are aromatic tetranuclear terpenoids with unprecedented carbon skeletons from Resina Commiphora and possess an uncommon 6/6/6/6 ring system. Compounds 458–465 have been identified as a series of totarane-type norditerpenes. Compounds 464–468 exhibit the rare characteristic of A-ring contraction, known as cephanolide A–C. Compound 469 possesses a skeleton of 17,19-dinorxeniaphyllane.

4. Chemical Constituents of C17 Norditerpenes

Seven major types of C17 norditerpenes have been reported in nature: the labdane type, abietane type, podocarpane type, briarane type, cassane type, cembrane type, and kaurane type. Additionally, there are other trinorditerpenes with special structures and some podocarpane dimers in nature (Table 11, Figure 13).

Table 11.

Chemical constituents of C17 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
470	baccaramione A	B. ramiflora	twigs	[146]
471	baccaramione B	B. ramiflora	twigs	[146]
472	baccaramione C	B. ramiflora	twigs	[146]
473	baccaramione D	B. ramiflora	twigs	[146]
474	euphorane B	E. dracunculoides	whole plants	[52]
475	12-hydroxy-16,17-bis-nor-simonellite	P. abrotanoides	roots	[48]
476	nimbidiol	P. abrotanoides	roots	[48]
477	16,17-bis-nor-multicauline	P. abrotanoides	roots	[48]
478	salyunnanin D	S. yunnanensis	roots	[121]
479	salyunnanin E	S. yunnanensis	roots	[121]
480	(5S,8R,10S)-20-nor-militibetin A	P. abrotanoides	roots	[48]
481	sessilifol P	C. sessilifolius	-	[59]
482	sessilifol Q	C. sessilifolius	-	[59]
483	(5S,7S,10R)-7-deoxy-7,18-epoxynimbidiol	C. sessilifolius	-	[48]
484	dihydroneotanshinlactone	S. digitaloides	roots	[122]
485	neotanshinlactone	S. digitaloides	roots	[122]
486	danshenspiroketallactone	S. digitaloides	roots	[122]
487	rubesanolides F	I. rubescens	leaves	[57]
488	rubesanolide G	I. rubescens	leaves	[57]
489	pinuyunnanacid O	P. yunnanensis	resins	[147]
490	flueggrene A	F. virosa	roots	[148]
491	flueggrene B	F. virosa	roots	[148]
492	epi-6-oxonimbidiol	C. angulatus	root bark and leaves	[149]
493	(+)-7-deoxynimbidiol	C. sessilifolius	-	[150]
494	celaphanol A	C. orbiculatus	-	[150,151]
495	angulatusphenol C	C. angulatus	root bark and leaves	[149]
496	angulatusphenol D	C. angulatus	root bark and leaves	[149]
497	angulatusphenol E	C. angulatus	root bark and leaves	[149]
498	△5-nimbidiol	C. angulatus	root bark and leaves	[149]
499	margosolone	C. angulatus	root bark and leaves	[149]
500	demethylnimbionol	C. angulatus	root bark and leaves	[149]
501	13,15-dihydroxypodocarpa-8,11,13-triene	P. banksiana Lamb	buds	[152]
502	(3R,5S,9R,10S)-3-hydroxy-ent-podocarpa-8(14)-ene-13-one	C. sessilifolius	-	[153]
503	(4R,5R,9R,10R,13S)-13-hydroxypodocarp-8(14)-en-19-oic acid	A. macrophylla	-	[6]
504	(4R,5R,9R,10R,13R)-13-hydroxypodocarp-8(14)-en-19-oic acid	A. macrophylla	-	[6]
505	13-oxo-podocarp-8(14)-en-19-oic acid	A. macrophylla	-	[6]
506	angulatusphenol A	C. angulatus	root bark and leaves	[149]
507	angulatusphenol B	C. angulatus	root bark and leaves	[149]
508	7′,8′-threo-guaiacylglycerol-α,γ-O-nimbidiol diether	C. sessilifolius	-	[150]
509	(M)-bicelaphanol A	C. orbiculatus	root bark	[151,154]
510	(P)-bicelaphanol A	C. orbiculatus	root bark	[151,154]
511	angulatusdiphenol A	C. angulatus	root bark and leaves	[149]
512	trolliusditerpenoside N	T. chinensis	flowers	[155]
513	enbepeanone A	A. grandiflflorum	-	[156]
514	caesalminaxin M	C. minax	seeds	[157]
515	populusone	P. euphratica	exudates	[158]
516	pharicusin B	I. pharicus	aerial parts	[159]
517	(±)-8,13-secoepicavernosine	Cacospongia sp.	-	[160]
518	(+)-8,13-secocavernosine	Cacospongia sp.	-	[160]
519	(−)-8,13-secocavernosine	Cacospongia sp.	-	[160]
520	(+)-cavernosine	Cacospongia sp.	-	[160]
521	(−)-cavernosine	Cacospongia sp.	-	[160]

Figure 13.

Structures of C17 norditerpenes.

4.1. Abietane

Compounds 470–477 are 15,16,17-bis-norditerpenes. Compound 479 is the 16-OH derivative of 478. Compound 480 represents a rare skeleton of a 20-nor-abietane. Compound 482 is defined as the C-7 epimer of compound 485, while compounds 484–486 are aromatic tetranuclear terpenoids with unprecedented carbon skeletons from S. digitaloides. Compounds 487–488 possess a unique γ-lactone subunit moiety positioned between C-8 and C-20, leading to the generation of the carbonyl carbon at C-13 through the degradation of the isopropyl group.

4.2. Podocarpane

Compounds 489–511 are trinorditerpenes of the podocarpane type. Compounds 509–510, existing as atropisomers, are two previously unknown dimeric trinorditerpenes separated from the root bark of C. orbiculatus. Compound 511 is a rare dimeric trinorditerpene with a 1,4-benzodioxane moiety.

4.3. Others

Compound 512 is a novel labdane-norditerpenoid glycoside with a six-membered epoxy system (8→13). Compound 513 is a novel norditerpene derived from a briarane skeleton. Compound 514 represents a previously unidentified trinorcassane diterpenoid bearing a dicyclic norditerpenoid with three acetoxy moieties. Compound 515 is determined to be a cembrane-type macrocyclic trinorditerpenoid with a fused 10/6 carbon skeleton. Compound 516 is a unique trinorditepenoid containing an unprecedented 20-epoxy-ent-kaurane skeleton. Compounds 517–521 are three pairs of unfrequent C17 γ-lactone norditerpenoid enantiomers.

5. Chemical Constituents of C16 Norditerpenes

Four main types of C16 norditerpenes have been found in nature: the labdane type, clerodane type, xeniaphyllane type, and abietane type. In addition to the common four types, there are also other norditerpenoids with unique structures and some dimers in nature sources (Table 12, Figure 14).

Table 12.

Chemical constituents of C16 norditerpenes.

No.	Name	Plant Source	Plant Organ	Ref.
522	acrostalic acid	P. sinensis	needles and twigs	[132,161]
523	LL-Z1271-β	A. wentii EN-48	-	[161,162]
524	13,14,15,16-tetranorlabda-8(17)-en-12-carboxylic acid	E. verrucosus	-	[4]
525	3α-hydroxy-8α-acetoxy-13,14,15,16-tetranorlabdan-12-oeic acid	S. aethiopis	aerial parts	[163]
526	avxanthin A	A. villosum	rhizomes	[164]
527	elettarin A	E. cardamomum	fruits	[165]
528	elettarin B	E. cardamomum	fruits	[165]
529	asperolide C	A. wentii EN-48	-	[162]
530	botryosphaerin B	P. sinensis	needles and twigs	[162]
531	asperolide A	A. wentii EN-48	-	[162,166]
532	asperolide B	A. wentii EN-48	-	[162,166]
533	asperolide E	A. wentii EN-48	culture extract	[166]
534	tetranorditerpenoid derivative	A. wentii EN-48	-	[162]
535	wentilactone A	A. wentii EN-48	-	[162]
536	wentilactone B	A. wentii EN-48	culture extract	[162]
537	13,14,15,16-tetranorlabd-7-en-19,6β:12,17-diolide	P. sinensis	needles and twigs	[161]
538	botryosphaerin G	P. sinensis	needles and twigs	[161]
539	botryosphaerin H	P. sinensis	needles and twigs	[161]
540	3α,10β-dimethyl-1,2,3,3a,5a,7,10b,10c-octahydro-5,8-dioxa-acephenanthrylene-4,9-dione	P. sinensis	needles and twigs	[161]
541	botryosphaerin A	P. sinensis	needles and twigs	[161]
542	1-naphthaleneacetic-7-oxo-1,2,3,4,4a,7,8,8a-octahydro1,2,4a,5-tetramethyl acid	P. longifolia	leaves	[167]
543	methyl-7-oxo-1,2,3,4,4a,7,8,8a-octahydro-1,2,4a,5-tetramethyl-1-naph-thaleneacetate	P. longifolia	leaves	[167]
544	castanol C	S. castanea	flowers	[50]
545	sinubatin A	S. nanolobata	-	[168]
546	norcrocrassinone	C. crassifolius	roots	[169]
547	norcrassin A	C. crassifolius	roots	[170]
548	(3aR,5S,5aR,6R,9aS,9bR)-methyl5-hydroxy-3α,6,9α-trimethyl-2oxododecahydronaphtho[21-b]furan-6-carboxylate	S. sahendica	leaves	[171]
549	acerolanin A	M. emarginata	aerial parts	[172]
550	acerolanin B	M. emarginata	aerial parts	[172]
551	acerolanin C	M. emarginata	aerial parts	[172]
552	trigonochinene E	T. flavidus	stems	[173]
553	vibsanolide F	V. odoratissimum	leaves	[174]
554	vibsanolide G	V. odoratissimum	leaves	[174]
555	trigoflavidol A	T. flavidus	stems	[173]
556	trigoflavidol B	T. flavidus	stems	[173]
557	neoboutomannin	T. flavidus	stems	[173]

Figure 14.

Structures of C16 norditerpenes.

5.1. Labdane

C16-labdane norditerpenes are common bicyclic diterpenes with four fewer carbon atoms. Compounds 522–525 are known as bicyclic norditerpenoids. Compound 525 is the first to be reported in nature. Compound 526 is a rare rearranged labdane-type tetranorditerpenoid with a fused tricarbocyclic system (6/6/5) and an α,β-unsaturated cyclopentenone unit in ring C. Compounds 527 and 528 represent a pair of new labdane-type tetranorditerpenoid epimers, which are the first known examples of naturally derived labdane tetranorditerpenoids. Compounds 531–541 are a series of tetracyclic tetranorlabdane diterpenoids.

5.2. Others

Compounds 542–543 exhibit clerodane-type tetranorditerpenoids. Compound 544 is a novel abietane tetranorditerpenoid, known as castanol C. Compound 545 possesses an unprecedented carbon skeleton derived from xeniaphyllane. Compound 546 is a newly reported tetranorditerpenoid featuring a special fused ring system of 6/6/5. Compound 547 is a new C16 tetranorditerpenoid lactone with an uncommon tetracyclic fuse system of 5/5/5/6. Compounds 549–551 possess an unprecedented framework of 2H-benz[e]inden-2-one. Compounds 552–553 represent a pair of epimers of vibsane-type tetranorditerpenes with a bicyclo[4.2.1]nonane unit. Compounds 555–556 comprise a pair of rearranged tetranorditerpenoid dimers with a spiroketal core moiety.

6. Pharmacological Activities

Norditerpene, a substance of profound pharmacological significance, manifests diverse primary pharmacological effects and biological activities encompassing cytotoxicity, anti-inflammatory activity, and antibacterial and antiviral actions, as well as antioxidant potential.

6.1. Cytotoxic activity

The anti-tumor activity of numerous norditerpenes has been extensively reported. The cytotoxicity of norditerpenes is the most frequently studied biological activity, and a table listing their cytotoxic activities is provided (Table 13). The cytotoxic activity of compound 208 was found to be the most potent against A549, Hela, and SGC-7901 cell lines, with IC₅₀ values of 0.10 µM, 0.13 µM, and 0.14 µM, respectively [78].

Table 13.

Cytotoxic activity of norditerpenes.

Name	Extraction Solvent	Cancer Types	Cancer Cells	Activities (IC50)	Ref.
tinocapillin A (38)	95% EtOH	liver cancer cervical cancer	HepG-2 Hela	9.9 ± 1.5 μM 9.7 ± 3.4 μM	[20]
tinocallone C (40)	95% EtOH	lung cancer	A549	14.0 ± 0.9 μM	[20]
tinocapillin B (41)	95% EtOH	lung cancer liver cancer cervical cancer	A549 HepG-2 Hela	9.6 ± 1.2 μM 10.1 ± 1.1 μM 12.0 ± 1.0 μM	[20]
icacinlactone F (76)	80% aqueous MeOH	breast cancer	MDA-MB-435 MDA-MB-231	6.16 μM 8.94 μM	[28]
asperether A (101)	EtOAc	breast duct cancer	T-47D	10 μM	[38]
asperether B (102)	EtOAc	breast cancer liver cancer	MCF-7 SMMC-7721	14 μM 12 μM	[38]
cryptotanshinone (148)	80% EtOH	colon cancer gastric cancer lung cancer	HCT-8 BGC-823 A549	3.9 μM 8.3 μM 2.6 μM	[44]
euphorane C (139)	95% EtOH	liver cancer	HepG-2	6.95 μM	[52]
methyltanshinoate (150)	acetone	liver cancer lung cancer breast cancer colon cancer	SMMC-7721 A549 MCF-7 SW-480	4.07 μM 5.26 μM 3.44 μM 6.35 μM	[50]
amentotaxin C (174)	MeOH	cervical cancer lung cancer breast cancer ovarian cancer liver cancer colon cancer	HeLa A549 MDA-MB-231 SKOV3 Huh-7 HCT-116	5.1 μM 9.8 μM 6.8 μM 2.9 μM 4.1 μM 1.9 μM	[65]
20-oxohainanolidol (205)	95% EtOH	leukemia lung cancer	HL-60 A549	0.77 ± 0.05 μM 1.129 ± 0.057 μM	[77]
cephinoid H (208)	MeOH	lung cancer cervical cancer gastric cancer	A549 HeLa SGC-7901	0.10 μM 0.13 μM 0.14 μM	[78]
10-hydroxyharringtonolide (223)	-	lung cancer oral epidermoid cancer leukemia colon cancer	A549 KB HL-60 HT-29	3.683 ± 0.947 μM 2.325 ± 0.040 μM 1.038 ± 0.002 μM 2.108 ± 0.108 μM	[79]
6-en-harringtonolide (229)	-	lung cancer oral epidermoid cancer leukemia colon cancer	A549 KB HL-60 HT-29	7.804 ± 3.797 μM 5.115 ± 0.148 μM 2.319 ± 0.247 μM 4.890 ± 0.622 μM	[79]
tanshinone I (393)	acetone	leukemia lung cancer breast cancer pancreatic cancer	HL-60 A549 SK-BR-3 PANC-1	3.19 μM 6.64 μM 3.40 μM 3.67 μM	[56,122]
dihydroisotanshinone I (394)	80% EtOH	lung cancer	A549	2.7 μM	[44]
dihydrotanshinone (395)	acetone	leukemia liver cancer lung cancer breast cancer pancreatic cancer	HL-60 SMMC-7721 A549 SK-BR-3 PANC-1	2.36 μM 3.03 μM 5.15 μM 3.97 μM 2.75 μM	[122]
3β-hydroxymakilactone A (424)	acetone	gastric cancer breast cancer liver cancer pancreatic cancer	AGS MDA-MB-231 HepG-2 PANC-1	0.88 ± 0.01 μM 5.46 ± 1.12 μM 5.56 ± 1.73 μM 1.35 ± 0.08 μM	[131]
2β-hydroxymakilactone A (425)	MeOH	cervical cancer gastric cancer breast cancer	Hela AGS MDA-MB-231	0.87 ± 0.04 μM 0.38 ± 0.03 μM 4.23 ± 2.06 μM	[131]
inumakilactone A (426)	MeOH	cervical cancer gastric cancer breast cancer	Hela AGS MDA-MB-231	1.77 ± 0.69 μM 1.33 ± 0.05 μM 2.98 ± 1.06 μM	[131]
inumakilactone B (428)	MeOH	cervical cancer gastric cancer breast cancer liver cancer pancreatic cancer	Hela AGS MDA-MB-231 HepG-2 PANC-1	0.62 ± 0.18 μM 0.55 ± 0.21 μM 0.66 ± 0.15 μM 3.54 ± 1.45 μM 8.51 ± 2.65 μM	[131]
dryperrein C (441)	95% EtOH	lung cancer leukemia	A549 HL-60	8.50 μM 1.95 μM	[136]
dryperrein D (442)	95% EtOH	leukemia	HL-60	1.37 μM	[136]
salyunnanin E (479)	acetone	cervical cancer	HeLa	0.86 μM	[121]
neotanshinlactone (485)	acetone	breast cancer	SK-BR-3	4.07 μM	[122]

6.2. Antimicrobial Activity

6.2.1. Antibacterial Activity

Inulifolinone D (16) from A. inulifolium can enhance the bactericidal activity against S. aureus. (MIC = 150–75 μg/mL) [10]. Actinomadurol (64) showed high antibacterial activity against pathogenic strains, including Staphylococcus aureus, Rhizophila Kocuria, and Proteus Hauseri, with MICs ranging from 0.39 to 0.78 μg/mL. However, Jbir-65 (63) did not exhibit any antibacterial activity, suggesting that the hydroxyl group at C-7 was responsible for antibacterial activity [25]. Compounds 69–72, 74, and 79–80 from I. Trichantha showed antibacterial activity against both standard and resistant strains of H. pylori, with an MIC of 8–64 μg/mL. In addition, compounds 72 and 74 showed superior antibacterial activity against H. pylori compared to other compounds, with MIC values ranging from 8 to 16 μg/mL. SAR studies have demonstrated that CH₃O-12 and 3, 20-epoxy moiety in 17-nor-pimarane diterpenes can function as activating groups, while the sugar moiety at C-2 might an inactivated group. The combination of antibiotic-icacinlactone B with either metronidazole or amoxicillin exhibited notable additive effects (FICI = 0.56–0.75) against the clinical strain HP159, suggesting that combination therapy has the potential to enhance antimicrobial activity, reduce dosage requirements, and mitigate adverse side effects. Compounds 87, 89, 96, 98, and 99 displayed inhibitory activities against E. tarda, M. luteus, P. aeruginosa, V. harveyi, and V. parahemolyticus, with MIC values of 4.0 μg/mL each; compounds 87 and 99 also exhibited activity against the F. graminearum, with MIC values of 2.0 and 4.0 μg/mL, respectively [34]. Compounds 90–91 exhibited comparable MIC values of 8.0 μg/mL against zoonotic pathogenic bacteria, including E. coli, E. tarda, V. harveyi, and V. parahaemolyticus. Compound 93 exhibited potent activity (MIC = 4.0 μg/mL) against the plant pathogen F. graminearum [35]. Salprzelactone (164) showed higher antibacterial activity against A. aerogenes than streptomycin, acheomycin, and ampicillin, as indicated by MIC values of 62.5 μg/mL versus 125 μg/mL, 250 μg/mL, and 125 μg/mL, respectively [55]. The growth of S. aureus was inhibited by citrinovirin (299) at an MIC of 12.4 μg/mL, while it displayed toxicity toward A. salina, with an LC₅₀ of 65.6 μg/mL. Moreover, compound 299 exhibited inhibitory effects ranging from 14.1% to 37.2% against C. Marina, H. Akashiwo, and P.donghaiense at 100 μg/mL; however, it stimulated the growth of S.trochoidea [101]. Compound 531 displayed potent activity against E. tarda, with an MIC value of 16 μg/mL [162,166]. Compounds 555–556 showed moderate antimicrobial activities against S. aureus, 8^#MRSA, and 82^#MRSA, with MIC values from 1.56 to 6.25 μg/mL [173].

6.2.2. Antifungal Activity

Compounds 333, 335, and 342 displayed antifungal activity against C. neoformans (MIC = 17.5, 12.5, and 10.0 μg/mL, respectively) and C. albicans (MIC = 20, 20, and 12.5 μg/mL, respectively) [116]. Compounds 333 and 342 also demonstrated inhibitory effects on the growth of P. destructans, with MIC values of 7.5 and 15 μg/mL, respectively [116]. Compound 534 showed moderate antifungal activities against C. albicans, with an MIC of 16 μg/mL [162].

6.2.3. Antiviral Activity

The compound eupneria J (118) displayed potent anti-HIV-1 activity (IC₅₀ = 0.31 μM). These findings suggest that the presence of a β-oriented hydroxyl group at C-4 may enhance its anti-HIV-1 activity. Furthermore, it is plausible that the acetoxyl group at C-18, rather than at C-3, contributes to an augmented anti-HIV effect [41]. Compound 276 exhibited antiviral activity against human enterovirus EV71, with an IC50 value of 5.0 μM [87]. Compound 394 exhibited anti-HBV activity by effectively suppressing the secretion of HBsAg and HBeAg, with IC50 values of 0.11 and 0.18 μM, respectively. In addition, it also effectively suppressed HBV DNA replication, with an SI value of 647.2 [56]. Compounds 422–423 showed potent anti-HCV activity, with EC50 values of 7.5 and 6.6 μM, respectively [128]. Compounds 490–491 demonstrated moderate anti-HCV activity, exhibiting EC50 values of 13.0 ± 0.3 μM and 23.6 ± 1.9 μM, respectively [148].

6.3. Anti-Inflammatory

The activation of NLRP3 inflammasome causes pyroptosis and results in the maturation of caspase-1 and the secretion of IL-1β [15]. The anti-NLRP3 inflammasome effects of compound 31 were evaluated by MCC950 (IC₅₀ = 23.1 ± 5.3 µM) as a positive control, which can specifically inhibit NLRP3 inflammasomes. Compound 31 inhibited IL-1β secretion (IC₅₀ = 5.5 ± 3.2 µM) and maturation of caspase-1 in a dose–dependent manner, indicating that cell pyroptosis is prevented, thereby demonstrating its ability to inhibit NLRP3 inflammasome activation [15].

Compound 82 derived from P. malabarica showed anti-inflammatory (anti-5-LOX) effects, with IC₅₀ values of 0.75 mg/mL, more potent than ibuprofen (IC₅₀ = 0.93 mg/mL). In vitro, compared with ibuprofen (selectivity index = 0.44), compound 82 exhibits a higher selectivity index (anti-COX-1_IC50/anti-COX-2_IC50 = 0.85), indicating fewer side effects. Notably, compound 82 exhibits promising potential against both cyclooxygenase and lipoxygenase [30].

The inhibitory potential of compound 279 against 5-LOX (IC₅₀ = 0.92 mg/mL) was found to be higher than ibuprofen (IC50 = 0.96 mg/mL) [89].

Compound 110 showed significant inhibition, with an IC₅₀ value of 14.7 ± 1.8 μM, surpassing the potency of PDTC (Pyrrolidinedithiocarbamate, IC₅₀ = 26.3 µM), a well-established positive control for an NF-κB inhibitor [39].

Compound 190 from C. sinensis exhibited effective inhibition of NF-κB activity (IC₅₀ 4.12 ± 0.61 µM) [73]. Salvialba acid (163) has been shown to possess anti-inflammatory effects on TNF-α-induced vascular inflammation in HAECs (human aortic endothelial cells) [60].

Compound 208, obtained from the twigs and leaves of C. fortune, dose–dependently inhibited TNF-α-induced NF-κB activation with an IC₅₀ value of 0.10 μM, which was similar to the inhibitory effect of the positive control MG132 (a proteasome inhibitor, IC₅₀ = 0.15 μM). These results suggest that the tropone moiety is important for the cytotoxicity and the inhibition of NF-κB signaling [78].

Compounds 255, 261, and 269 also displayed inhibitory effects on NF-κB with inhibitory rates of 28.6%, 25.1%, and 12.5% in a dose of 50 µM compared to the positive control PDTC (IC₅₀ = 37 µM) [82,86].

Compounds 494–496 and 500 demonstrated moderate inhibitory activities against NF-κB activation in RAW264.7 macrophages, with IC₅₀ values of 15, 25, 19, and 4 μM, respectively [149,150,151]. Compound 8 was the most effective compound in inhibiting LPS-induced nitric oxide (NO) production (IC₅₀ = 3.56 μM) in T. orientalis. Moreover, it attenuated the expression of iNOS and COX-2 at both mRNA and protein levels by inhibiting LPS-induced degradation of I-κBα and activation of NF-κB, as well as reducing ERK phosphorylation [7].

Compounds 324 and 325 exerted pronounced inhibition of NO production in LPS-induced macrophages (RAW 264.7), with IC₅₀ values of 7.50 and 6.49 μM, respectively [113].

Compound 437 showed a significant anti-inflammatory effect on LPS-induced NO production in RAW264.7 cells (IC₅₀ = 21.0 μM) [12].

Compounds 445–448 showed potent inhibitory activity against LPS-induced production of NO and TNF-α in RAW264.7 cells, with IC₅₀ values of below 25 µM [40,137].

Compounds 373, 374, 378, and 480 exhibited potent inhibition of NO release in the cell culture medium of LPS-stimulated macrophages. Furthermore, they significantly inhibited iNOS expression in J774A.1 macrophages at doses of 50–12.5 μM [122].

Compounds 493 and 508 exhibited potent inhibitory effects on LPS-stimulated NO releases and pro-inflammatory mediators, with IC₅₀ values of 4.9 and 12.60 μM, respectively, by suppressing iNOS and COX-2 expressions to prevent NO production [139]. 13-epi-scabrolide C (263) inhibited the production of IL-12 and IL-6 in LPS-stimulated BMDCs (bone marrow-derived cells, IC₅₀ = 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively). This suggests that the C-13 methoxyl moiety may play an important role in anti-inflammatory activity [82].

Scrodentoids H,I (307–308) exert anti-inflammatory effects by reducing LPS-induced inflammation and inhibiting the JNK/STAT3 pathway in macrophages. STAT proteins play a pivotal role in modulating cytokine-mediated inflammatory responses, and STAT3 is highly correlated with inflammatory responses. In response to inflammatory stimuli, STAT3 acts as a transcription factor that directly governs the expression of pro-inflammatory cytokines. Scrodentoids H and I might be beneficial in the treatment of inflammatory diseases, like ulcerative colitis and atherosclerotic diseases [105].

Sinusiaetone A (316) from S. siaesensis exhibited significant inhibition against LPS-induced inflammation in BV-2 microglia at a concentration of 20 μM and also decreased the mRNA levels of pro-inflammatory cytokines IL-6 and IL-1β [109].

6.4. Antioxidative Activity

Compound 82 showed antioxidant activity comparable to α-tocopherol, exhibiting an IC₅₀ value of approximately 0.6 mg/mL for DPPH scavenging activity, and it can serve as a natural alternative to synthetic antioxidants [30].

The radical quenching analysis revealed that compound 279 exhibited a higher antioxidant activity (IC₅₀ value of 0.60 mg/mL) compared to α-tocopherol. This suggests the potential of compound 279 as a natural antioxidant in future applications, attributed to its low hydrophobicity and spatial variability [89].

6.5. α-Glucosidase Inhibitory Activity

Compounds 2, 298, and 363 displayed an inhibitory effect on α-glucosidase and were evaluated by p-nitro-phenyl-α-D-glucopyranoside as the substrate and acarbose as a positive control. Compound 2 showed a moderate inhibition, with IC₅₀ values of 282 μM, surpassing the efficacy of the positive control acarbose (1.33 mM) [2]. Compound 298 displayed significant inhibition, with an IC₅₀ value of 64.05 ± 1.59 μg/mL [100]. Compound 363 showed a moderate inhibition on α-glucosidase (IC₅₀ = 7.94 μM). At the same time, the inhibition kinetics of compound 363 were studied via a noncompetitive inhibition mechanism, and the inhibition kinetics parameter (Ki) was 10.8 μM [120].

6.6. Cell Proliferation Activity

Compounds 100, 477, and 473 exhibited inhibitory effects on concanavalin A-induced T cell proliferation (IC₅₀ = 13.6, 1.66, and 2.09 μM, respectively), as well as lipopolysaccharide-induced B cell proliferation (IC₅₀ = 22.4, 1.37, and 3.31 μM, respectively), without exhibiting any obvious cytotoxicity to T cells and B cells [37,146]. Compounds 258 and 261 showed strong inhibitory activities against Con A-induced T lymphocyte proliferation, with IC₅₀ values of 23.7 and 8.69 μM, respectively. The remarkable enhancement in activity can be attributed to the configurational inversion at C-5 in compound 261 [81].

Compound 515 has been confirmed to promote the proliferation and differentiation of umbilical cord-derived mesenchymal stem cells into keratinocyte-like cells at a concentration of 10 μM [158].

6.7. Other Activities

Compounds 34, 43, and 55 demonstrated the NGF-mediated promotion of neurite outgrowth on PC12 cells at a concentration of 10 μM [17]. Compound 509 showed a potent neuroprotective effect against a hydrogen peroxidation-induced reduction in cell viability in PC12 cells at a concentration of 1 μM [151,154]. Compound 58 displayed the most effective inhibitory effect on osteoclast differentiation, exhibiting IC₅₀ values of 0.7 μM. It downregulated the expression levels of osteoclast-related genes and promoted the apoptosis of osteoclasts. Compounds 58–60 inhibited osteoclast formation, with IC₅₀ ranging from 0.7 to 4.0 μM, thereby demonstrating their antiosteoporosis effects [23]. Compounds 95–97 showed potent biological activities against some marine organisms. Compound 97 was highly toxic to A. salina, with an LC₅₀ value of 6.36 μM. Moreover, compound 96 displayed significant toxicity toward C. marina and H. akashiwo (LC₅₀ = 0.81 and 2.88 μM, respectively), while compound 95 exhibited higher effectiveness against Alexandrium sp., with an LC₅₀ value of 8.73 μM [36]. Compounds 143 and 152–154 selectively inhibited BChE, with IC₅₀ values of 2.4, 7.9, 50.8, and 0.9 µM, respectively. Moreover, compounds 143 and 154 moderately inhibited AChE, with IC₅₀ values of 329.8 μM and 342.9 μM, respectively [54]. Compounds 249–252 effectively inhibited Th17 differentiation, exhibiting IC₅₀ values ranging from 2 to 18.07 μM. Compounds 250–251 were more effective than the positive control digoxin, which is a classical inhibitor of Th17 differentiation [80]. Compound 364 inhibited the acetyl transfer activity of M. tuberculosis GlmU, with an IC₅₀ value of 41.85 μM, representing a novel therapeutic target for tuberculosis [120]. Compound 371 can significantly inhibit the formation of macrophage foam cells induced by oxidized low-density lipoprotein, suggesting its potential as a protective agent against atherosclerosis [134]. Compounds 454–456 displayed antifobrotic activities on TGF-β1-induced rat renal proximal tubular cells, effectively attenuating the excessive production of collagen I and α-SMA [141]. Compound 505 exhibited inhibitory activities against PTP1B and was a moderate time-dependent inactivator of PTP1B, with k_i value of 0.11 M⁻¹ s⁻¹ [6]. Compound 539 exhibited a mortality rate of 30% in P. redivivus and 28% in C. elegans within a 24 h period at a concentration of 400 mg/L, whereas the control group (5% acetone) only resulted in a mortality rate of 1.5% during the same time frame [161]. The anti-AD activity of compound 547 was comparatively weaker than memantine (p < 0.05), and it can be regarded as an anti-AD compound candidate [170].

7. Conclusions

This review summarized 557 compounds among C19, C18, C17, and C16 norditerpenes from 2010–2023. Obviously, C19 norditerpenes are the characteristic and main bioactive components of norditerpenes. Lamiaceae plants contain abundant norditerpenes, especially Isodon and Salvia genera. The Lamiaceae plant Salvia miltiorrhiza possesses abundant C19 norditerpenes, and the Cephalotaxaceae plant Cephalotaxus fortunei possesses abundant cephalotane-type norditerpenes.

Most norditerpenes exhibited anti-tumor, anti-inflammatory, anti-bacterial, and antioxidant properties, as well as inhibitory effects against HIV and α-glucosidase. Recent research suggests that norditerpenes may be a possibility for the future development of anti-tumor drugs. For example, euphorane C (139) inhibited the proliferation of K562 cells (IC₅₀ = 3.59 µM) and provided the possibility for developing anti-leukemia drugs. Cephinoid H (208) isolated from C. fortunei showed the strongest cytotoxic activities, with IC₅₀ values of 0.10, 0.13, and 0.14 µM against cell lines A549, Hela, and SGC-7901, respectively. It can be used as a candidate drug for treating various types of cancer. In Table 14, most norditerpenes have inhibitory effects on lung cancer, breast cancer, and cervical cancer cells. We should find appropriate targets to explore their mechanisms and focus on their in vivo activities in the future. With the rapid development of nanomaterials, we can combine effective norditerpenoids with them to improve their targeting and efficacy. Due to antibiotic resistance and side effects, it is meaningful to discover new antibiotics. Actinomadurol (64) has good antibacterial activity and provides the possibility for the discovery of antibiotics. At the same time, the structure–activity relationship was studied, which found that the hydroxyl group at C-7 affected antibacterial activity. CH₃O-12 and the 3,20-epoxy moiety in 17-nor-pimarane diterpenes can function as activating groups, while the sugar moiety at C-2 might be an inactivated group. This is beneficial for the design and synthesis of new antibacterial drugs. Norditerpenes produce anti-inflammatory effects by influencing recognized markers of inflammatory processes such as IF, NO levels, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-alpha (TGF-α). In the future, norditerpenes may be a useful and safe method for treating inflammatory diseases, such as rheumatoid arthritis, and can play a similar role as ibuprofen and dexamethasone.

Table 14.

Anti-inflammatory activity of norditerpenes.

Name	Pathways	Activities (IC50)	Ref.
callinteger B (31)	Inhibited IL-1β secretion and maturations of caspase-1 in a dose-dependent manner	9.9 ± 1.5 μM	[15]
18(4→14), 19(4→8)-bis-abeo-nor-isopimarane-1,5-diene-3-yl-3β-methoxy propyl pentanoate (82)	Inhibited of pro-inflammatory cyclooxygenases (COX-2, COX-1) and 5-lipoxygenase (5-LOX) enzymes	0.75 mg/mL	[30]
6-((E)-12-(furan-13-yl)-10-methylpent-10-en-9-yl)-6,7,8,8atetrahydro-3H-isochromen-1-(5H)-one (279)	Inhibited of 5-LOX enzymes	0.92 mg/mL	[89]
(2S,3R,5S,9S,10S,13S)-2-O-E-cinnamoyl-3-hydroxy-16-nor-ent-pimar-8(14)-en-15-oic acid (110)	Inhibited the NF-κB pathway in LPS-stimulated RAW264.7 cells	14.7 ± 1.8 μM	[39]
cephalotanin A (190)	Evaluated in an NF-kB pathway luciferase assay for inhibitory effects	4.12 ± 0.61 µM	[73]
salvialba acid (163)	Lowered the levels of ICAM-1 and VCAM-1 in HAECs induced by TNF-α	20 µM caused significant reductions in cell viability; 0.05, 0.5, 5, and 10 µM did not affect cell viability	[60]
cephinoid H (208)	Inhibited TNF-α-induced NF-κB activation	0.10 μM	[78]
5-epi-sinuleptolide (255)	Activated ARE expression and inhibited NO production and NF-κB expression in RAW264.7 macrophage cells	5.6 ± 0.2 µM 57.9 ± 0.4 µM 28.6 ± 0.2 µM	[82,86]
sinuleptolide (261)	Activated ARE expression and inhibited NO production and NF-κB expression in RAW264.7 macrophage cells	3.6 ± 0.3 µM 56.0 ± 0.3 µM 25.1 ± 0.5 µM	[82,86]
fragilolide A (269)	Activated ARE expression and inhibited NO production and NF-κB expression in RAW264.7 macrophage cells	1.2 ± 0.2 µM 27.8 ± 0.6 µM 12.5 ± 0.2 µM	[82,86]
celaphanol A (494)	Demonstrated moderate inhibitory activities against NF-κB activation in RAW264.7 macrophages	15 μM	[149,150,151]
angulatusphenol C (495)	Demonstrated moderate inhibitory activities against NF-κB activation in RAW264.7 macrophages	25 μM	[149,150,151]
angulatusphenol D (496)	Demonstrated moderate inhibitory activities against NF-κB activation in RAW264.7 macrophages	19 μM	[149,150,151]
demethylnimbionol (500)	Demonstrated moderate inhibitory activities against NF-κB activation in RAW264.7 macrophages	4 μM	[149,150,151]
15-nor-14-oxolabda-8(17),13(16)-dien-19-oic acid (8)	Inhibited LPS-induced nitric oxide (NO) production. Attenuated the expression of iNOS and COX-2 at both mRNA and protein levels by inhibiting the LPS-induced degradation of I-κBα and the activation of NF-κB, as well as reducing ERK phosphorylation	3.56 μM	[7]
ebractenoid A (324)	Inhibited the production of NO in LPS-induced macrophages	7.50 μM	[113]
ebractenoid B (325)	Inhibited the production of NO in LPS-induced macrophages	6.49 μM	[113]
hedychin F (437)	Inhibited the production of NO in LPS-induced macrophages	21.0 μM	[12]
flickinflimilin B (445)	Inhibited the production of NO and TNF-α in LPS-induced macrophages	<25.0 μM	[40,137]
flickinflimilin A (446)	Inhibited the production of NO and TNF-α in LPS-induced macrophages	<25.0 μM	[40,137]
norflickinflimiod E (447)	Inhibited the production of NO and TNF-α in LPS-induced macrophages	<25.0 μM	[40,137]
norflickinflimiod F (448)	Inhibited the production of NO and TNF-α in LPS-induced macrophages	<25.0 μM	[40,137]
przewalskin (373)	Inhibited iNOS expression in J774A.1 macrophages stimulated with LPS	-	[48]
(5S,6S,7R,10R)-16,17-bis-nor-6β-hydroxy-18,7-epoxyferruginol (374)	Inhibited iNOS expression in J774A.1 macrophages stimulated with LPS	-	[48]
(5S,10R)-16,17-bis-nor-pisiferanol (378)	Inhibited iNOS expression in J774A.1 macrophages stimulated with LPS	-	[48]
(5S,8R,10S)-20-nor-militibetin A (480)	Inhibited iNOS expression in J774A.1 macrophages stimulated with LPS	-	[48]
(+)-7-deoxynimbidiol (493)	Inhibited LPS-stimulated NO releases and pro-inflammatory mediators and suppressed iNOS and COX-2 expressions to prevent NO production	4.9 μM	[139]
7′,8′-threo-guaiacylglycerol-α,γ-O-nimbidiol diether (508)	Inhibited LPS-stimulated NO releases and pro-inflammatory mediators, suppressed iNOS and COX-2 expressions to prevent NO production	12.6 μM	[139]
13-epi-scabrolide C (263)	Inhibited the production of IL-12 and IL-6 in LPS-stimulated BMDCs	5.30 ± 0.21 μM 13.12 ± 0.64 μM	[82]
scrodentoid H (307)	Reduced LPS-induced inflammation and inhibited the JNK/STAT3 pathway in macrophages	-	[105]
scrodentoid I (308)	Reduced LPS-induced inflammation and inhibited the JNK/STAT3 pathway in macrophages	-	[105]
sinusiaetone A (316)	Inhibited LPS-induced inflammation in BV-2 microglia at a concentration of 20 μM and decreased the mRNA levels of pro-inflammatory cytokines IL-6 and IL-1β	-	[109]

Although current research has shown that these compounds exhibit various biological activities, most of the research mainly focuses on in vitro cell activity assays. It is necessary to investigate their in vivo activities. Further clinical trials are crucial to confirm the pharmacological effects of norditerpenes in order to fully illustrate their therapeutic effects on diseases. We hope that this review can promote research on norditerpenes.

Abbreviations

A549	Human non-small cell lung cancer cells
AGS	Human gastric adenocarcinoma cells
ARE	Antioxidant response element
BGC-823	Human gastric adenocarcinoma cells
BMDCs	Bone marrow-derived cells
COXs	Cyclooxygenases
Con A	Knife-beetle protein A
ED50	Median effective dose
GlmU	GlcNAc-P uridyltransferase
HepG2	Human hepatocellular carcinoma cells
Hela	Human cervical carcinoma cells
Huh-7	Human hepatocellular carcinoma cells
HL-60	Human promyelocytic leukemia cells
HT-29	Human colon cancer cells
HCTs	Human colon cancer cells
HAECs	Human aortic endothelial cells
iNOS	Inducible nitric oxide synthase
IC50	50% inhibiting concentration
ICAM-1	Intercellular adhesion molecule-1
ILs	Interleukins
JNK	c-Jun NH2-terminal kinase
KBs	Human oral epidermoid carcinoma cells
LPS	Lipopolysaccharide
MIC	Minimum inhibitory concentration
MCF-7	Human breast cancer cells
MDA-MB	Triple-negative breast cancer cells
MG132	A proteasome inhibitor
NF-κB	Nuclear factor kappa B
NO	Nitric oxide
NGF	Nerve growth factor
PANC-1	Human pancreatic cancer cells
PDTC	Pyrrolidinedithiocarbamate
SMMC-7721	Human hepatocarcinoma cells
SW-480	Human colon cancer cells
SGC-7901	Human stomach cancer cells
SK-BR-3	Human breast cancer cells
SKOV3	Human ovarian cancer cells
STAT	Signal transducers and activators of transcription
T-47D	Human breast duct cancer cells
TNF-α	Tumor necrosis factor-α
TCM	Traditional Chinese medicine
VCAM-1	Vascular cell adhesion molecule-1

Author Contributions

Conceptualization and writing the manuscript draft, N.Z.; data analysis, Q.Z.; collecting the references, Q.Y. and G.F.; writing—review and editing, W.S.; project administration and funding acquisition, W.W. and B.L. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Source databases for these publications include the Science Citation Index (SCI), SCI Expanded.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding Statement

This work was supported by the National Natural Science Foundation of China (grant Nos. 82074122 and 82174078); the Ungraduated Students Research Innovative Program of Hunan University of Chinese Medicine (grant No. 2022CX71); Key Research and Development Programs of Hunan Science and Technology Department (grant No. 2023SK2046); Research Foundation of Education Bureau of Hunan Province (grant No. 23A0280).