(1R,4S,8R,9R,12S,13S,14R,16S,17R,19R)-17-[(Ethyl­sulfan­yl)meth­yl]-9,14-di­hydroxy-7,7-dimethyl-2,18-dioxo-3,10-dioxapenta­cyclo[14.2.1.01,13.04,12.08,12]nona­decan-19-yl acetate acetone solvate

Hao Shi; Hong Xiang Sun

doi:10.1107/S1600536808043341

. 2008 Dec 24;65(Pt 1):o202. doi: 10.1107/S1600536808043341

(1R,4S,8R,9R,12S,13S,14R,16S,17R,19R)-17-[(Ethylsulfanyl)methyl]-9,14-dihydroxy-7,7-dimethyl-2,18-dioxo-3,10-dioxapentacyclo[14.2.1.0^1,13.0^4,12.0^8,12]nonadecan-19-yl acetate acetone solvate

Hao Shi ^a,^*, Hong Xiang Sun ^b

PMCID: PMC2968108 PMID: 21581657

Abstract

The title compound, C₂₄H₃₂O₈S·C₃H₆O, features three six-membered and two five-membered rings. The six-membered rings adopt chair, boat and slightly distorted boat conformations whereas one five-membered ring adopts an approximate envelope conformation and the other a twist conformation. Disorder was modelled for the ethylthio group with the ethyl-C atoms resolved over three positions with occupancies of 0.58 (4), 0.23 (4) and 0.19 (3). In the crystal, an O—H⋯O hydrogen bond links the molecules into chains.

Related literature

For puckering parameters, see: Cremer & Pople (1975 ▶). For related literature, see: Yamaguchi et al. (1977 ▶); Chen et al. (1987 ▶); He et al. (2007 ▶); Shi et al. (2007 ▶).

Experimental

Crystal data

C₂₄H₃₂O₈S·C₃H₆O
M _r = 538.63
Orthorhombic,
a = 10.6258 (12) Å
b = 11.4825 (18) Å
c = 22.265 (2) Å
V = 2716.6 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.17 mm⁻¹
T = 298 (2) K
0.53 × 0.32 × 0.28 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T _min = 0.915, T _max = 0.954
11871 measured reflections
4774 independent reflections
3201 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.112
S = 1.04
4774 reflections
373 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.23 e Å⁻³
Absolute structure: Flack (1983 ▶), 2053 Friedel pairs
Flack parameter: 0.00 (12)

Data collection: SMART (Bruker, 1999 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808043341/tk2336sup1.cif

e-65-0o202-sup1.cif^{(30.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808043341/tk2336Isup2.hkl

e-65-0o202-Isup2.hkl^{(233.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O5—H5⋯O8ⁱ	0.82	2.16	2.952 (4)	161

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Symmetry code: (i) Inline graphic .

Acknowledgments

This research was supported by the Natural Science Foundation of Zhejiang Province (grant No. Y205318) and the Open Foundation of Key Disciplines within Zhejiang Province.

supplementary crystallographic information

Comment

Since the natural product diterpenoid Macrocalyxin J exhibits cytotoxicity against cultures of Hela cells (Shi et al., 2007), the title compound (1), a derivative, was synthesised for investigation. The molecule of (1) is composed of three six-membered and two five-membered rings, Fig. 1. The cyclohexane ring A (C4—C8/C12) adopts a chair conformation with puckering parameters (Cremer & Pople, 1975) Q = 0.525 (4) Å, θ = 156.0 (4)° and φ = 275.2 (10)°. Ring B (O3/C2/C1/C13/C12/C4) exists in a distorted boat conformation (Q = 0.671 (3) Å, θ = 109.0 (3)° and φ = 94.9 (3)°) and ring C (C1/C13—C16/C19) adopts a boat conformation (Q = 0.851 (3) Å, θ = 79.9 (2) and φ = 296.0 (2)°). The five-membered ring D (C1/C18/C17/C16/C19) is twisted on C(16)/C(19), and five-membered ring E (O10/C9/C8/C12/C11) adopts an envelope conformation with C(12) displaced by 0.500 (5)Å from the mean plane of the remaining four atoms. The stereochemistry of the A/B ring juncture is trans, and at the B/C ring juncture, cis. With the C1, C19 and C16 atoms being located in both rings C and D, an α-configuration is adopted to avoid steric crowding; no evidence was found in this study for the synthesis of the β-configuration. The main difference between (1) and macrocalyxin J (He et al., 2007) is found in ring D. In the latter, the equivalent ring D is conjugated, i.e. is a α-methylenecyclopentanone ring. It has been reported that the α-methylenecyclopentanone group in the Rabdosia diterpenes is highly reactive toward sulfhydryl groups, essential to enzyme function (Yamaguchi et al., 1977). This observation is ascribed to the steric strain within the five-membered ring which increases the reactivity of the conjugated double bond (Chen et al., 1987). Compound (1) was characterised as an acetone solvate. In the crystal structure the constituent molecules are connected via hydrogen bonding, Table 1.

Experimental

Compound (1) was obtained in a two-step syntheses, Scheme 1. In an ice-water bath, Jones reagent (0.2 ml ) was added to a solution of Macrocalyxin J (200 mg; isolated from Rabdosia macrocalyx) in acetone (20 ml). After stirring for 20 min, the solution was filtered and added to 15% NaHCO₃ in water (120 ml). The mixture was extracted 3 times with diethyl ether (90 ml). After evaporation of the solvent, a white residue was isolated. Recrystallization from methanol gave 19-acetyloxy-10,13-dideoxy-5-hydroxy-10-oxo, (5β,19R)-enmain (175.6 mg) (2), see Scheme. Into an ethanol solution (50 ml) of (2) (150 mg) was added dropwise excess ethanethiol (0.5 ml). After stirring at room temperature for 3 h, the mixture was concentrated in vacuo to give an oily residue, which was washed with water (2.0 ml), then recrystallized from CH₃COCH₃ to afford (1) as colorless crystals (127.3 mg).