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. 2020 Jan 21;5(4):1813–1821. doi: 10.1021/acsomega.9b02986

Efficient and Highly Stereoselective Syntheses of (+)-proto-Quercitol and (−)-gala-Quercitol Starting from the Naturally Abundant (−)-Shikimic Acid

Xing-Liang Zhu †, Lei Wang †, Yong-Qiang Luo †, Yun-Gang He †, Feng-Lei Li †, Mian-Mian Sun †, Shi-Ling Liu ‡,*, Xiao-Xin Shi †,*
PMCID: PMC7003206  PMID: 32039317

Abstract

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Efficient and highly stereoselective syntheses of (+)-proto-quercitol and (−)-gala-quercitol starting from the naturally abundant (−)-shikimic acid were described in this article. (−)-Shikimic acid was first converted to the key intermediate by eight steps in 53% yield. It was then converted to (+)-proto-quercitol by three steps in 78% yield and was also converted to (−)-gala-quercitol by five steps in 63% yield. In summary, (+)-proto-quercitol and (−)-gala-quercitol were synthesized from (−)-shikimic acid by 11 and 13 steps in 41 and 33% overall yields, respectively.

1. Introduction

(+)-proto-Quercitol 1 and (−)-gala-quercitol 2 (Figure 1) belong to the family of cyclohexanepentanols named “quercitols” (a subclass of cyclitols).1 There are 16 stereoisomeric members in the family, of which 12 optically active isomers are grouped into six pairs of enantiomers and four other isomers are symmetric (or meso).2 (+)-proto-Quercitol 1 exists in nature; it can be isolated from many plant species.3 Several asymmetric syntheses of (+)-proto-quercitol 1 from (−)-quinic acid,4 (+)-inositol,5 and some chiral intermediates6 have been reported. (−)-gala-Quercitol 2 is non-natural. It cannot be obtained from nature, but some asymmetric syntheses of (−)-gala-quercitol 2 from (−)-quinic acid4b,7 and other chiral starting materials8 have also been reported. To explore the potential usage of (+)-proto-quercitol 1, (−)-gala-quercitol 2, and the derivatives in drug discovery for controlling diabetes and related diseases,3b,3d,9 development of efficient and practical asymmetric syntheses of these two target molecules is a promising and challenging task in the pharmaceutical industry for chemists.

Figure 1.

Figure 1

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Three related compounds.

(−)-Shikimic acid (Figure 1) has captured worldwide attention10 in recent decades due to its use in the synthesis of the neuraminidase inhibitor oseltamivir-phosphate (Tamiflu, a drug for the treatment of avian flu).11 Many researchers have tried to improve production of (−)-shikimic acid via natural extraction,10a microbial engineering,10e,10g and chemical synthesis.10a,12 (−)-Shikimic acid is found in many plant species10a,10f,13 and is noted to be in particularly high abundance in Chinese star anise (Illicium verum).10f,14 The Chinese star anise is a popular flavoring material for foods in China, so it is annually planted in many areas and is readily available in large quantities. (−)-Shikimic acid has become a highly prospective molecule in the pharmaceutical industry due to the development of new methods for rapid and high-yielding extraction15 from Chinese star anise. We have recently been engaged in developing novel syntheses of oseltamivir-phosphate11a,11b,11d,11f,11g and some other pharmaceutically valuable molecules,16 and herein we want to disclose highly diastereoselective, efficient, and practical syntheses of (+)-proto-quercitol 1 and (−)-gala-quercitol 2 by using the commercially available and inexpensive (−)-shikimic acid as the starting material.

2. Results and Discussion

The novel total synthesis of (+)-proto-quercitol 1 starting from (−)-shikimic acid is depicted in Scheme 1. As can be seen from Scheme 1, esterification of (−)-shikimic acid first produced methyl (−)-shikimate 3 in 97% yield. Next, when compound 3 was exposed to 2,2-dimethoxypropane (2,2-DMP) and catalytic p-toluenesulfonic acid (TsOH) in ethyl acetate at room temperature (rt), two cis vicinal hydroxyls were protected by an acetonide moiety to give compound 4 in 95% yield. Reaction of compound 4 with benzoyl chloride (BzCl), triethylamine, and catalytic 4-diaminopyridine (DMAP) in dichloromethane at 0 °C to room temperature furnished benzoate 5 in 96% yield. RuCl3-catalyzed stereoselective dihydroxylation17 of the α,β-unsaturated ester 5 in a mixed solvent of acetonitrile, ethyl acetate, and water (CH3CN/EtOAc/H2O = 3:3:1) at −5 °C produced compound 6 in 88% yield. During the stereoselective dihydroxylation of compound 5, ruthenium catalyst coordinated with the double bond in the opposite direction of the acetonide moiety due to its high steric hindrance, so that two hydroxyls at C-1 and C-2 should have the desired upward orientation. Compound 6 was then exposed to tert-butyl-dimethylsilyl chloride (TBDMSCl), triethylamine, and imidazole in dichloromethane under refluxing; the less hindered secondary hydroxy at C-2 was selectively protected by the TBDMS group to afford compound 7 in 92% yield.

Scheme 1. Total Synthesis of (+)-proto-Quercitol 1 Starting from (−)-Shikimic Acid.

Scheme 1

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Subsequently, when compound 7 was treated with NaBH4 in a mixed solvent of dichloromethane and methanol (CH2Cl2/CH3OH = 3:1) at room temperature, COOMe at C-1 could be selectively reduced due to the binding of the α-hydroxy group with NaBH4,16a,18 and pinacol 8 was thus obtained in 89% yield. Oxidative cleavage of the vicinal diols of compound 8 with NaIO4 in aqueous acetonitrile (CH3CN/H2O = 10:1) at room temperature produced ketone 9 in 92% yield. Compound 9 was then treated with NaBH4 at 0 °C in a mixed solvent of ethyl acetate and water (EtOAc/H2O = 4:1); the carbonyl group was stereoselectively reduced to furnish compound 10 in 90% yield, which was contaminated with only a trace amount (<1%) of its epimer. Conformational analysis for this highly stereoselective reduction is shown in Figure 2; compound 9 would probably adapt to a boat conformation in which two bulky groups (OTBDMS and OBz) at C-2 and C-5 are in equatorial positions, and then the borohydride anion would attack the carbonyl group from the upward direction to avoid repulsion between BH4– and the acetonide moiety. The silyl protective group (TBDMS) could be removed by treatment of compound 10 with Bu4NF in tetrahydrofuran to produce compound 11 in 93% yield. The acetonide moiety was then selectively removed by treatment of compound 11 with hydrochloride acid (HCl) at room temperature in a mixed solvent of ethyl acetate and water (EtOAc/H2O = 10:1) to afford compound 12 in 92% yield, and the ester group (OBz) kept intact during the reaction at room temperature. Finally, compound 12 was exposed to ammonia in methanol at room temperature to furnish (+)-proto-quercitol 1 in 91% yield.

Figure 2.

Figure 2

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Conformational analysis for reduction of 9 to 10.

The novel total synthesis of (−)-gala-quercitol 2 starting from (−)-shikimic acid is depicted in Scheme 2. As can be seen from Scheme 2, compound 10 was first obtained from (−)-shikimic acid by the same eight steps in 53% overall yield as per Scheme 1. Compound 10 was then exposed to methanesulfonyl chloride (MsCl), triethylamine, and catalytic DMAP in dichloromethane at 0 °C to produce methanesulfonate 13 in 95% yield. When compound 13 was treated with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) and acetic acid in toluene under refluxing according to a previous report,19 an SN2-type substitution took place to furnish compound 14 in 87% yield. An (S) configuration of the chiral center at C-1 was inversed to an (R) configuration during this SN2-type substitution. For the configuration inversion at C-1 of compound 10, we have also tried the Mitsunobu reaction20 with various acids (PhCOOH, 4-NO2-PhCOOH, AcOH, and CF3COOH) as nucleophiles, but the yields were moderate. Subsequently, the silyl protective group (TBDMS) was removed by treatment of compound 14 with Bu4NF in tetrahydrofuran at room temperature to produce compound 15 in 92% yield. The acetonide moiety was then removed by treatment of compound 15 with water and trifluoracetic acid (CF3COOH) at room temperature to produce compound 16 in 92% yield. Finally, compound 16 was exposed to ammonia at room temperature to afford (−)-gala-quercitol 2 in 90% yield.

Scheme 2. Total Synthesis of (−)-gala-Quercitol 2 Starting from (−)-Shikimic Acid.

Scheme 2

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In addition, the stereochemistries of compounds 10 and 14 have also been further confirmed by the 2D NMR technique. 1H–1H NOESY spectra of compounds 17 (the acetate of compound 10) and 14 are shown in Figure 3. As can be seen from the 1H–1H NOESY spectrum of compound 14, there are NOE correction spots between H-1 and H-5, meaning that protons on C-1 and C-5 have the cis relationship, and thus the chiral center at C-1 of compound 14 has an (S) configuration. Moreover, as can be seen from the 1H–1H NOESY spectrum of compound 17, there are NOE correction spots between H-1 and H-3, meaning that protons on C-1 and C-3 have the cis relationship, and thus the chiral center at the C-1 position of compound 17 has an (R) configuration.

Figure 3.

Figure 3

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1H–1H NOESY spectra of 14 and 17.

3. Conclusions

In conclusion, we have performed stereoselective total syntheses of (+)-proto-quercitol 1 and (−)-gala-quercitol 2 starting from the naturally abundant (−)-shikimic acid. (+)-proto-Quercitol 1 has been synthesized starting from the naturally abundant (−)-shikimic acid by 11 steps in 41% overall yield with >99% purity; (−)-gala-quercitol 1 has also been synthesized starting from (−)-shikimic acid by 13 steps in 33% overall yield with >99% purity. The above total syntheses might be more practical than the other synthetic approaches described in the literature4−8 due to some advantages such as high overall yields, good cost effectiveness, as well as mild reaction conditions and simple experimental procedures for all steps. In addition, the stereochemistries of compounds 14 and 17 (acetate of compound 10) have been unequivocally confirmed by analyses of their 1H–1H NOESY spectra.

4. Experimental Section

4.1. General Method

1H NMR and 13C NMR spectra were acquired on a Bruker AM-400 instrument; chemical shifts are given on the δ scale as parts per million (ppm) with tetramethylsilane (TMS) as the internal standard. Infrared (IR) spectra were recorded with a Nicolet Magna IR-550 instrument. Mass spectra were performed with an HP1100 LC-MS spectrometer. Melting points were determined on a Mel-TEMP II apparatus. Column chromatography was performed on silica gel (Qingdao Ocean Chemical Corp.). All chemicals were analytically pure.

4.2. Methyl Shikimate 3

(−)-Shikimic acid (20.00 g, 114.8 mmol) and anhydrous methanol (400 mL) were added into a round-bottom flask, which was equipped with a stirrer bar. After the mixture was stirred and cooled to 0 °C by an ice bath, thionyl chloride (6.840 g, 57.50 mmol) was dropwise added into the flask over 10 min. The ice bath was removed, and the mixture was then heated and stirred under refluxing (60 °C) for 3 h. Charcoal (3 g) was added, and the mixture was further stirred at 60 °C for 1 h. The mixture was cooled to room temperature and then filtered by suction to remove charcoal. The filtrate was concentrated under vacuum to dryness to give the crude solid product. A mixed solvent of ethyl acetate (150 mL) and hexane (100 mL) was added, and the mixture was triturated and stirred for 2 h. The suspension was filtered to afford methyl shikimate 3 (20.96 g, 111.4 mmol) as white crystals in 97% yield. Mp 114–116 °C {lit.21 mp 112–113 °C}. [α]D25 = −127.3 (c 1.9, EtOH) {lit.21 [α]D = −125 (c 1.8, EtOH)}. 1H NMR (400 MHz, DMSO-d6) δ 2.06 (dd, J1 = 16.0 Hz, J2 = 3.9 Hz, 1H, H-6α), 2.39–2.48 (m, 1H, H-6β), 3.55–3.61 (m, 1H), 3.67 (s, 3H, OCH3), 3.84–3.88 (m, 1H), 4.18–4.26 (m, 1H), 4.66 (br s, 1H, OH), 4.84 (br s, 1H, OH), 4.86 (br s, 1H, OH), 6.62–6.64 (m, 1H, H-2). 13C NMR (DMSO-d6) δ 166.70, 139.77, 127.31, 70.00, 66.75, 65.38, 51.51, 29.60. MS (EI) m/z (%): 188 (M+, 1), 156 (17), 139 (8), 138 (17), 129 (29), 111 (12), 110 (15), 97 (100), 96 (18), 83 (8), 69 (19), 53 (6), 41 (5). IR (KBr film) ν 3343, 2956, 2904, 1719, 1665, 1435, 1244, 1096, 1069, 927, 749 cm–1.

4.3. Methyl (3R,4S,5R)-3,4-O-Isopropylidene Shikimate 4

Compound 3 (20.00 g, 106.3 mmol) and ethyl acetate (200 mL) were added into a round-bottom flask, which was equipped with a stirrer bar. 2,2-Dimethoxypropane (33.24 g, 319.2 mmol) and p-toluenesulfonic acid (1.830 g, 10.63 mmol) were added, and the mixture was stirred at room temperature for 3 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:1), an aqueous solution of potassium carbonate (25 mL, 5% w/w) was added, and the mixture was further stirred for 10 min. The mixture was transferred into a separatory funnel. The two phases were separated, and the organic phase was washed with brine (20 mL) and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:3) to afford compound 4 (23.06 g, 101.0 mmol) as a colorless oil in 95% yield. [α]D25 = −77.4 (c 1.5, CHCl3). 1H NMR (400 MHz, CDCl3) δ 1.39 (s, 3H), 1.43 (s, 3H), 2.18–2.27 (m, 1H, H-6α), 2.78 (dd, J1 = 17.4 Hz, J2 = 4.6 Hz, 1H, H-6β), 3.74 (s, 3H, OCH3), 3.84–3.91 (m, 1H), 4.07 (dd, J1 = 7.5 Hz, J2 = 6.3 Hz, 1H), 4.71–4.75 (m, 1H), 6.88–6.92 (m, 1H, H-2). 13C NMR (CDCl3) δ 166.60, 133.98, 130.56, 109.71, 77.87, 72.24, 68.72, 52.16, 29.36, 27.96, 25.73. HRMS (ESI) calcd for C11H16O5Na [M + Na]+: 251.0895. Found: 251.0888. IR (neat) ν 3454, 2988, 2934, 1719, 1655, 1439, 1375, 1248, 1054, 859, 755 cm–1.

4.4. Methyl (3R,4S,5R)-3,4-O-Isopropylidene-5-O-benzoyl Shikimate 5

Compound 4 (10.00 g, 43.81 mmol), triethylamine (8.860 g, 87.56 mmol), and 4-dimethylamino-pyridine (535.0 mg, 4.380 mmol) were dissolved in dichloromethane (100 mL). The solution was cooled to 0 °C by an ice bath, and benzoyl chloride (8.013 g, 57.01 mmol) was added dropwise over 10 min. The ice bath was removed, and the mixture was further stirred at room temperature for 5 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:3), dichloromethane was removed by vacuum distillation. Ethyl acetate (200 mL) and an aqueous solution (50 mL, 10% w/w) were added. After the mixture was stirred for 2 h, the two phases were separated by a separatory funnel. The organic phase was washed with brine (20 mL) and then dried over anhydrous MgSO4. The organic solution was concentrated under vacuum to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:4) to afford compound 5 (13.99 g, 42.09 mmol) as a colorless oil in 96% yield. [α]D25 = −62.5 (c 1.2, CHCl3). 1H NMR (400 MHz, CDCl3) δ 1.41 (s, 3H), 1.44 (s, 3H), 2.53 (dd, J1 = 17.8 Hz, J2 = 6.0 Hz, 1H, H-6α), 2.85–2.93 (m, 1H, H-6β), 3.78 (s, 3H, OCH3), 4.40 (dd, J1 = 7.8 Hz, J2 = 7.9 Hz, 1H), 4.79–4.84 (m, 1H), 5.44–5.51 (m, 1H), 6.96–6.99 (m, 1H, H-2), 7.43 (dd, J1 = 7.8 Hz, J2 = 8.0 Hz, 2H), 7.56 (t, J = 7.8 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 166.46, 165.65, 134.43, 133.22, 129.72, 129.03, 128.38, 110.11, 73.81, 71.92, 70.22, 52.16, 27.89, 26.40, 26.10. HRMS (ESI) calcd for C18H20O6Na [M + Na]+: 355.1158. Found: 355.1154. IR (neat) ν 2987, 2936, 1722, 1658, 1602, 1451, 1437, 1251, 1112, 1069, 1030, 858, 713 cm–1.

4.5. Methyl (1S,2R,3R,4S,5R)-5-Benzoyloxy-1,2-dihydroxy-3,4-isopropylidenedioxy-cyclohexane-1-carboxylate 6

Sodium periodate (6.774 g, 31.67 mmol), ruthenium trichloride (87.5 mg, 0.422 mmol), and water (10 mL) were added into a round-bottom flask, which was equipped with a stirrer bar. The mixture was stirred at room temperature for 15 min, and the color changed to bright yellow. Compound 5 (7.006 g, 21.08 mmol) was dissolved in a mixed solvent of ethyl acetate (30 mL) and acetonitrile (30 mL), and the resulting solution was cooled to −5 °C by a salt ice bath. The above-obtained bright-yellow aqueous viscous solution was added, and the mixture was further stirred at −5 °C for 1 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:3), ethyl acetate (100 mL) and a saturated aqueous solution of Na2S2O3 (80 mL) were added. The mixture was vigorously stirred for 15 min, and then the two phases were separated by a separatory funnel. The aqueous solution was extracted twice with ethyl acetate (2 × 60 mL). Organic extracts were combined, washed with brine (20 mL), and then dried over anhydrous MgSO4. The organic solution was concentrated under vacuum to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:2) to afford compound 6 (6.803 g, 18.57 mmol) as white crystals in 88% yield. Mp 147–149 °C. [α]D25 = −8.6 (c 2.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ 1.39 (s, 3H), 1.55 (s, 3H), 1.99 (dd, J1 = 15.0 Hz, J2 = 6.9 Hz, 1H, H-6α), 2.61 (dd, J1 = 15.0 Hz, J2 = 5.9 Hz, 1H, H-6β), 3.86 (s, 3H, OCH3), 4.04 (d, J = 7.8 Hz, 1H, H-2), 4.36 (dd, J1 = 7.6 Hz, J2 = 7.8 Hz, 1H), 4.50 (dd, J1 = 7.6 Hz, J2 = 7.2 Hz, 1H), 5.45–5.50 (m, 1H, H-5), 7.45 (dd, J1 = 8.2 Hz, J2 = 8.0 Hz, 2H), 7.57 (t, J = 8.0 Hz, 1H), 8.06 (d, J = 8.2 Hz, 2H). 13C NMR (CDCl3) δ 174.53, 165.72, 133.23, 129.84, 129.83, 128.38, 109.80, 77.66, 76.45, 76.43, 73.57, 69.66, 53.46, 35.42, 27.72, 25.49. HRMS (ESI) calcd for C18H22O8Na [M + Na]+: 389.1212. Found: 389.1210. IR (KBr film) ν 3494, 3063, 2993, 2937, 1735, 1715, 1602, 1452, 1381, 1277, 1115, 1073, 884, 714 cm–1.

4.6. Methyl (1S,2R,3S,4S,5R)-5-Benzoyloxy-2-(tert-butyldimethylsilyloxy)-3,4-isopropylidenedioxy-1-hydroxy-cyclohexane-1-carboxylate 7

Compound 6 (5.008 g, 13.67 mmol) was dissolved in dichloromethane (50 mL). Triethylamine (4.150 g, 41.01 mmol), imidazole (930.0 mg, 13.66 mmol), and tert-butyldimethylsilyl chloride (16.53 g, 109.7 mmol) were added. The mixture was heated to reflux and was further stirred for 48 h. The solution was concentrated by vacuum distillation, and then ethyl acetate (60 mL) and an aqueous solution of potassium carbonate (30 mL, 10% w/w) were added. The mixture was vigorously stirred for 10 min, and then the two phases were separated by a separatory funnel. The aqueous solution was extracted twice with ethyl acetate (2 × 50 mL). Organic extracts were combined, washed with brine (20 mL), and then dried over anhydrous MgSO4. The organic solution was concentrated under vacuum to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:4) to afford compound 7 (6.046 g, 12.58 mmol) as white crystals in 92% yield. Mp 82–84 °C. [α]D25 = −14.6 (c 2.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ 0.05 (s, 3H), 0.15 (s, 3H), 0.86 (s, 9H), 1.35 (s, 3H), 1.50 (s, 3H), 1.92 (dd, J1 = 14.9 Hz, J2 = 7.5 Hz, 1H, H-6α), 2.66 (dd, J1 = 14.9 Hz, J2 = 6.8 Hz, 1H, H-6β), 3.78 (s, 3H, OCH3), 4.11 (d, J = 7.0 Hz, 1H, H-2), 4.27 (dd, J1 = 7.0 Hz, J2 = 6.9 Hz, 1H), 4.51 (dd, J1 = 6.9 Hz, J2 = 6.8 Hz, 1H), 5.34–5.38 (m, 1H, H-5), 7.42 (dd, J1 = 7.8 Hz, J2 = 8.0 Hz, 2H), 7.55 (t, J = 7.8 Hz, 1H), 8.06 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 174.25, 165.91, 133.10, 129.96, 129.86, 128.32, 109.28, 78.24, 77.49, 76.33, 75.42, 69.80, 52.89, 35.15, 27.72, 25.69, 25.41, 17.95, −4.10, −5.55. HRMS (ESI) calcd for C24H36O8SiNa [M + Na]+: 503.2077. Found: 503.2080. IR (KBr film) ν 3516, 3066, 2932, 2857, 1725, 1602, 1452, 1373, 1270, 1221, 1098, 838, 713 cm–1.

4.7. (1R,2R,3S,4S,5R)-5-Benzoyloxy-2-(tert-butyl-dimethylsilyloxy)-1-hydroxy-1-hydroxymethyl-3,4-isopropylidenedioxy Cyclohexane 8

Compound 7 (5.003 g, 10.41 mmol) was dissolved in a mixed solvent of dichloromethane (60 mL) and methanol (20 mL). Sodium borohydride (1.980 g, 52.34 mmol) was added in portions over 3 h. After the addition was finished, the mixture was further stirred for 3 h. The solution was concentrated under vacuum; ethyl acetate (80 mL) and water (60 mL) were added. After the mixture was vigorously stirred for 15 min, the two phases were separated by a separatory funnel. The aqueous solution was extracted twice with ethyl acetate (2 × 50 mL). Organic extracts were combined and dried over anhydrous MgSO4. The solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:2) to afford compound 8 (4.193 g, 9.277 mmol) as white crystals in 89% yield. Mp 88–90 °C. [α]D25 = −35.8 (c 2.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ 0.17 (s, 3H), 0.20 (s, 3H), 0.93 (s, 9H), 1.35 (s, 3H), 1.50 (s, 3H), 1.80 (dd, J1 = 14.2 Hz, J2 = 10.4 Hz, 1H, H-6α), 2.28 (dd, J1 = 14.2 Hz, J2 = 5.9 Hz, 1H, H-6β), 3.53 (d, J = 11.0 Hz, 1H), 3.62 (d, J = 11.0 Hz, 1H), 3.95 (d, J = 6.4 Hz, 1H, H-2), 4.32 (dd, J1 = 6.4 Hz, J2 = 6.6 Hz, 1H), 4.50 (dd, J1 = 6.6 Hz, J2 = 6.8 Hz, 1H), 5.13–5.21 (m, 1H, H-5), 7.43 (dd, J1 = 7.8 Hz, J2 = 8.0 Hz, 2H), 7.57 (t, J = 7.8 Hz, 1H), 8.06 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 166.11, 133.10, 129.98, 129.80, 128.31, 109.50, 78.43, 76.46, 73.52, 73.40, 71.24, 67.16, 34.56, 27.59, 25.93, 25.23, 18.18, −4.08, −5.08. HRMS (ESI) calcd for C23H36O7SiNa [M + Na]+: 475.2128. Found: 475.2128. IR (KBr film) ν 3461, 3250, 2988, 2931, 1724, 1603, 1453, 1381, 1274, 1115, 1069, 856, 717 cm–1.

4.8. (2R,3S,4S,5R)-5-Benzoyloxy-2-(tert-butyldimethyl-silyloxy)-3,4-isopropylidenedioxy Cyclohexan-1-one 9

Compound 8 (5.005 g, 11.06 mmol) was dissolved in a mixed solvent of acetonitrile (100 mL) and water (10 mL). Sodium periodate (3.553 g, 16.61 mmol) was added, and the mixture was stirred at room temperature for 3 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:3), ethyl acetate (150 mL) and a saturated aqueous solution of Na2SO3 (80 mL) were added. The mixture was vigorously stirred for 15 min, and then the two phases were separated by a separatory funnel. The aqueous solution was extracted twice with ethyl acetate (2 × 50 mL). Organic extracts were combined, washed with brine (20 mL), and then dried over anhydrous MgSO4. The organic solution was concentrated under vacuum to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:4) to afford compound 9 (4.280 g, 10.18 mmol) as white crystals in 92% yield. Mp 98–99 °C. [α]D25 = −28.3 (c 2.1, CHCl3) 1H NMR (400 MHz, CDCl3) δ 0.10 (s, 3H), 0.15 (s, 3H), 0.93 (s, 9H), 1.40 (s, 3H), 1.54 (s, 3H), 2.52 (dd, J1 = 17.1 Hz, J2 = 8.2 Hz, 1H, H-6α), 3.01 (dd, J1 = 17.1 Hz, J2 = 4.9 Hz, 1H, H-6β), 4.31–4.36 (m, 2H), 4.45–4.52 (m, 1H), 5.59–5.66 (m, 1H, H-5), 7.43 (dd, J1 = 7.9 Hz, J2 = 8.1 Hz, 2H), 7.58 (t, J = 7.9 Hz, 1H), 8.02 (d, J = 8.1 Hz, 2H). 13C NMR (CDCl3) δ 203.53 (C = O), 165.47 (COO), 133.45, 129.89, 129.33, 128.42, 110.31, 79.56, 78.41, 75.62, 70.16, 39.54, 27.45, 25.72, 25.12, 18.50, −4.69, −5.19. HRMS (ESI) calcd for C22H32O6SiNa [M + Na]+: 443.1866. Found: 4743.1864. IR (KBr film) ν 3060, 2934, 2858, 1727, 1603, 1461, 1379, 1268, 1105, 1067, 875, 840, 774, 706 cm–1.

4.9. (1R,2S,3S,4S,5R)-5-Benzoyloxy-2-(tert-butyl-dimethylsilyloxy)-1-hydroxy-3,4-isopropylidenedioxy Cyclohexane 10

Compound 9 (2.005 g, 4.767 mmol) was dissolved in ethyl acetate (20 mL). After the solution was cooled to 0 °C by an ice bath, an aqueous solution of sodium borohydride (543.5 mg, 14.37 mmol) in water (5 mL) was slowly added in 15 min. The mixture was then stirred at 0 °C for 2 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:3), ethyl acetate (30 mL) and water (30 mL) were added. The mixture was vigorously stirred for 15 min, and then the two phases were separated by a separatory funnel. The aqueous solution was extracted twice with ethyl acetate (2 × 30 mL). Organic extracts were combined, washed with brine (20 mL), and then dried over anhydrous MgSO4. The solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:3) to afford compound 10 (1.814 g, 4.292 mmol) as white crystals in 90% yield. [α]D25 = −8.7 (c 6.8, CHCl3) 1H NMR (400 MHz, CDCl3) δ 0.14 (s, 3H), 0.18 (s, 3H), 0.92 (s, 9H), 1.35 (s, 3H), 1.53 (s, 3H), 1.96–2.05 (m, 1H, H-6α), 2.10–2.18 (m, 1H, H-6β), 3.69 (dd, J1 = 6.8 Hz, J2 = 6.2 Hz, 1H), 3.79–3.85 (m, 1H), 4.09 (dd, J1 = 6.2 Hz, J2 = 5.8 Hz, J = 5.8 Hz, 1H), 4.25 (dd, J1 = 6.2 Hz, J2 = 6.4 Hz, 1H), 5.57–5.61 (m, 1H, H-5), 7.44 (dd, J1 = 7.7 Hz, J2 = 8.0 Hz, 2H), 7.56 (t, J = 7.7 Hz, 1H), 8.03 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 165.30, 133.26, 129.83, 129.72, 128.43, 109.42, 79.88, 77.40, 76.23, 69.61, 68.81, 31.28, 28.17, 26.32, 25.90, 18.15, −4.21, −4.87. HRMS (ESI) calcd for C22H34O6SiNa [M + Na]+: 445.2022. Found: 445.2017. IR (KBr film) ν 3446, 2987, 2931, 2856, 1724, 1637, 1462, 1382, 1270, 1098, 838, 780, 713 cm–1.

4.10. (1R,2S,3R,4S,5R)-5-Benzoyloxy-1,2-dihydroxy-3,4-isopropylidenedioxy Cyclohexane 11

Compound 10 (2.005 g, 4.745 mmol) was dissolved in tetrahydrofuran (20 mL). Tetrabutylamonium fluoride (4.960 g, 18.97 mmol) was added, and the reaction mixture was then stirred at room temperature for 30 min. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:2), the solvent was removed by vacuum distillation. Ethyl acetate (30 mL) and water (30 mL) were added. The mixture was vigorously stirred for 15 min, and then the two phases were separated by a separatory funnel. The aqueous solution was extracted twice with ethyl acetate (2 × 20 mL). Organic extracts were combined, washed with brine (20 mL), and then dried over anhydrous MgSO4. The solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:2) to afford compound 11 (1.362 g, 4.417 mmol) as white crystals in 93% yield. Mp 177–178 °C. [α]D25 = +20.6 (c 1.7, CH3OH). 1H NMR (400 MHz, CDCl3) δ 1.37 (s, 3H), 1.55 (s, 3H), 1.93–2.04 (m, 1H, H-6α), 2.17–2.25 (m, 1H, H-6β), 3.65 (dd, J1 = 7.7 Hz, J2 = 7.5 Hz, 1H), 3.86–3.94 (m, 1H), 4.16 (dd, J1 = 7.5 Hz, J2 = 5.6 Hz, 1H), 4.22–4.26 (m, 1H), 5.60–5.65 (m, 1H, H-5), 7.44 (dd, J1 = 7.6 Hz, J2 = 8.0 Hz, 2H), 7.58 (t, J = 7.6 Hz, 1H), 8.00 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 165.11, 133.45, 129.69, 129.54, 128.52, 109.90, 79.58, 77.68, 75.71, 69.17, 67.63, 32.40, 28.14, 26.22. HRMS (ESI) calcd for C16H20O6Na [M + Na]+: 331.1158. Found: 331.1153. IR (KBr film) ν 3445, 3066, 2956, 2932, 1719, 1694, 1604, 1454, 1370, 1261, 1211, 1092, 1064, 1048, 891, 838, 756, 711 cm–1.

4.11. (1R,2S,3R,4R,5R)-5-Benzoyloxy-1,2,3,4-tetra-hydroxy Cyclohexane 12

Compound 11 (2.004 g, 6.500 mmol) was dissolved in ethyl acetate (50 mL). Concentrated hydrochloric acid (2.5 mL, 36.5% w/w) and water (2.5 mL) were added. The mixture was stirred at room temperature for 3 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:2), ethyl acetate (50 mL) and powdered anhydrous potassium carbonate (5.528 g, 40.00 mmol) were added. After the mixture was stirred for 1 h, the mixture was filtered to remove inorganic salts. The filtrate was concentrated under vacuum to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:2) to afford compound 12 (1.604 g, 5.979 mmol) as white crystals in 92% yield. Mp 197–198 °C. [α]D25 = −13.4 (c 2.4, CH3OH). 1H NMR (400 MHz, DMSO-d6) δ 1.79–1.95 (m, 2H, two H-6), 3.41–3.51 (m, 2H), 3.53–3.61 (m, 1H), 3.78–3.81 (m, 1H), 5.05–5.08 (m, 1H, H-5), 7.51 (dd, J1 = 7.5 Hz, J2 = 7.7 Hz, 2H), 7.64 (t, J = 7.5 Hz, 1H), 7.92 (d, J = 7.7 Hz, 2H). 13C NMR (DMSO-d6) δ 164.68, 133.41, 129.69, 129.09, 128.77, 74.13, 72.22, 71.87, 69.66, 69.07, 32.04. HRMS (ESI) calcd for C13H16O6Na [M + Na]+: 291.0845. Found: 291.0845. IR (KBr film) ν 3406, 2963, 2929, 1713, 1601, 1453, 1280, 1110, 1068, 710 cm–1.

4.12. (+)-proto-Quercitol 1

Compound 12 (1.002 g, 3.735 mmol) was dissolved in methanol (20 mL). Concentrated ammonia (5 mL) was added. The mixture was stirred at room temperature for 48 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 2:1), charcoal (1.0 g) was added, and the mixture was further stirred for 1 h. The mixture was filtered by suction, and the filtrate was concentrated to dryness by vacuum distillation to give the crude solid product. A mixed solvent of ether (20 mL) and pure water (15 mL) was added and stirred for 5 min. The two phases were separated, and the aqueous phase was washed twice with ether (2 × 20 mL). The aqueous solution was concentrated to dryness by vacuum distillation. Toluene (15 mL) was added and then removed by vacuum distillation. Toluene (15 mL) was added again and then removed again by vacuum distillation. Finally, (+)-proto-quercitol 1 (558.0 mg, 3.399 mmol) as off-white crystals was obtained in 91% yield (>99% purity). Mp 236–238 °C {lit.5 238–239 °C}. [α]D25 = +24.8 (c 0.5, H2O) {lit.6a [α]D = +23.2 (c 0.2, H2O)}. 1H NMR (400 MHz, D2O) δ 1.72 (ddd, J1 = 14.3 Hz, J2 =11.4 Hz, J3 = 2.9 Hz, 1H, H-6α), 1.89 (ddd, J1 = 14.1 Hz, J2 = 4.0 Hz, J3 = 4.2 Hz, 1H, H-6β), 3.47 (dd, J1 = 9.3 Hz, J2 = 9.1 Hz, 1H), 3.58–3.70 (m, 2H), 3.80–3.84 (m, 1H), 3.91–3.94 (m, 1H). 13C NMR (D2O) δ 77.50, 75.17, 73.89, 71.84, 71.53, 36.21. HRMS (ESI) calcd for C6H12O5Na [M + Na]+: 187.0582. Found: 187.0581. IR (KBr film) ν 3314, 2931, 2906, 1419, 1074, 1047, 600 cm–1.

4.13. (1R,2R,3S,4S,5R)-5-Benzoyloxy-2-(tert-butyl-dimethylsilyloxy)-3,4-isopropylidenedioxy-1-methane-sulfonyloxy Cyclohexane 13

Compound 10 (2.004 g, 4.742 mmol), triethylamine (960.0 mg, 9.487 mmol), and 4-dimethylaminopyridine (58.0 mg, 0.475 mmol) were dissolved in dichloromethane (20 mL). The solution was cooled to 0 °C by an ice bath. Methanesulfonyl chloride (815.0 mg, 7.115 mmol) was slowly added, and the mixture was stirred at 0 °C for 1 h. After dichloromethane was removed by vacuum distillation, ethyl acetate (60 mL) and an aqueous HCl solution (1 M, 10 mL) were added. The mixture was vigorously stirred for 5 min, and then the two phases were separated by a separatory funnel. The organic phase was washed with an aqueous solution of potassium carbonate (10% w/w, 10 mL) and then was dried over anhydrous MgSO4. The solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:5) to afford compound 13 (2.256 g, 4.506 mmol) as a colorless oil in 95% yield. [α]D25 = +4.8 (c 3.1, CHCl3). 1H NMR (400 MHz, CDCl3) δ 0.15 (s, 3H), 0.17 (s, 3H), 0.93 (s, 9H), 1.37 (s, 3H), 1.54 (s, 3H), 2.22–2.30 (m, 1H, H-6α), 2.32–2.40 (m, 1H, H-6β), 3.08 (s, 3H, CH3 in Ms), 4.05 (dd, J1 = 6.8 Hz, J2 = 5.0 Hz, 1H), 4.17 (dd, J1 = 5.0 Hz, J2 = 5.2 Hz, 1H), 4.30 (dd, J1 = 5.4 Hz, Hz, J2 = 5.2 Hz, 1H), 4.72–4.79 (m, 1H, H-1), 5.49–5.56 (m, 1H, H-5), 7.46 (dd, J1 = 7.8 Hz, J2 = 8.0 Hz, 2H), 7.58 (t, J = 7.8 Hz, 1H), 8.04 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 165.45, 133.38, 129.77, 129.57, 128.49, 109.74, 79.90, 78.24, 75.55, 72.65, 69.36, 38.90, 30.20, 28.02, 26.20, 25.80, 18.05, −4.58. HRMS (ESI) calcd for C23H36O8SSiNa [M + Na]+: 523.1798. Found: 523.1799. IR (KBr film) ν 3070, 2925, 2854, 1723, 1604, 1462, 1383, 1273, 1238, 1109, 1064, 835, 712 cm–1.

4.14. (1S,2S,3S,4S,5R)-1-Acetoxy-5-benzoyloxy-2-(tert-butyldimethylsilyloxy)-3,4-isopropylidenedioxy Cyclohexane 14

Acetic acid (722.5 mg, 12.03 mmol) and DBU (915.0 mg, 6.010 mmol) were dissolved in toluene (3 mL). After the solution was stirred under refluxing for 1 h, compound 13 (1.003 g, 2.005 mmol) was added. The mixture was further stirred at reflux for 2 h. After the mixture was cooled to room temperature, ethyl acetate (50 mL) and an aqueous HCl solution (1 M, 10 mL) were added. The mixture was vigorously stirred for 10 min, and then the two phases were separated by a separatory funnel. The organic phase was washed with an aqueous solution of potassium carbonate (10% w/w, 15 mL) and then was dried over anhydrous MgSO4. The solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:5) to afford compound 14 (811.0 mg, 1.745 mmol) as a colorless oil in 87% yield. [α]D25 = −44.4 (c 1.1, CHCl3). 1H NMR (500 MHz, CDCl3) δ 0.10 (s, 3H), 0.12 (s, 3H), 0.93 (s, 9H), 1.36 (s, 3H), 1.55 (s, 3H), 2.05 (s, 3H, CH3 in Ac), 2.08–2.14 (m, 2H, two H-6), 4.19 (dd, J1 = 5.4 Hz, J2 = 3.8 Hz, 1H), 4.26 (dd, J1 = 3.8 Hz, J2 = 4.0 Hz, 1H), 4.32 (dd, J1 = 6.2 Hz, J2 = 4.0 Hz, 1H), 5.11–5.18 (m, 1H, H-1), 5.29–5.31 (m, 1H, H-5), 7.42 (dd, J1 = 7.8 Hz, J2 = 8.1 Hz, 2H), 7.55 (t, J = 7.8 Hz, 1H), 8.04 (dd, J = 8.1 Hz, 2H). 13C NMR (CDCl3) δ 169.93, 165.69, 133.05, 130.03, 129.77, 128.28, 109.86, 78.35, 76.61, 72.76, 69.68, 68.79, 28.05, 27.97, 26.14, 25.69, 21.15, 18.08, −4.89, −4.92. HRMS (ESI) calcd for C24H36O7SiNa [M + Na]+: 487.2128. Found: 487.2128. IR (neat) ν 3066, 2955, 2857, 1746, 1723, 1603, 1453, 1373, 1274, 1239, 1109, 1064, 834, 779, 712 cm–1.

4.15. (1S,2S,3R,4S,5R)-1-Acetoxy-5-benzoyloxy-3,4-isopropylidenedioxy-2-hydroxy Cyclohexane 15

Compound 14 (1.005 g, 2.163 mmol) was dissolved in tetrahydrofuran (10 mL). Tetraethylammonium floride (2.265 g, 8.663 mmol) was added, and the mixture was stirred at room temperature for 30 min. After tetrahydrofuran was removed by vacuum distillation, ethyl acetate (30 mL) and water (20 mL) were added. The mixture was vigorously stirred for 5 min, and then the two phases were separated by a separatory funnel. The aqueous solution was extracted again with ethyl acetate (20 mL). Organic extracts were combined and dried over anhydrous MgSO4. The solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:3) to afford compound 15 (698.0 mg, 1.992 mmol) as a colorless oil in 92% yield. [α]D25 = −15.9 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3) δ 1.37 (s, 3H), 1.54 (s, 3H), 2.07 (s, 3H, CH3 in Ac), 2.07–2.13 (m, 1H, H-6α), 2.17–2.25 (m, 1H, H-6β), 4.18–4.22 (m, 1H), 4.34–4.42 (m, 2H), 5.20–5.25 (m, 1H), 5.27–5.34 (m, 1H), 7.43 (dd, J1 = 7.8 Hz, J2 = 8.0 Hz, 2H), 7.55 (t, J = 7.8 Hz, 1H), 8.04 (d, J1 = 8.0 Hz, 2H). 13C NMR (CDCl3) δ 169.99, 165.62, 133.19, 129.87, 129.73, 128.34, 109.70, 77.24, 76.13, 71.81, 70.07, 68.86, 28.26, 27.96, 25.97, 21.08. HRMS (ESI) calcd for C18H22O7Na [M + Na]+: 373.1263. Found: 373.1262. IR (neat) ν 3451, 3026, 2924, 2853, 1721, 1694, 1656, 1592, 1439, 1375, 1262, 1164, 1121, 809, 744 cm–1.

4.16. (1S,2R,3R,4R,5R)-1-Acetoxy-5-benzoyloxy-2,3,4-trihydroxy Cyclohexane 16

Compound 15 (502.5 mg, 1.434 mmol) was dissolved in dichloromethane (5 mL). Trifluoroacetic acid (2.5 mL) and water (0.25 mL) were added. The mixture was stirred at room temperature for 20 min. The solvent was removed by vacuum distillation to give the crude product, which was immediately purified by flash chromatography (eluent: EtOAc/hexane = 1:1) to afford compound 16 (410.0 mg, 1.321 mmol) as white crystals in 92% yield. Mp 159–161°C. [α]D25 = −9.0 (c 1.2, CH3OH). 1H NMR (400 MHz, DMSO-d6) δ 1.86 (dd, J1 =18.5 Hz, J2 = 11.3 Hz, 1H, H-6α), 1.95 (s, 3H, CH3 in Ac), 1.96–2.01 (m, 1H, H-6β), 3.78–3.81 (m, 1H), 3.82–3.87 (m, 2H), 4.95–5.10 (m, 2H), 7.51 (dd, J1 = 7.9 Hz, J2 = 8.1 Hz, 2H), 7.64 (t, J = 7.9 Hz, 1H), 7.98 (d, J = 8.1 Hz, 2H). 13C NMR (DMSO-d6) δ 169.81, 165.38, 133.15, 130.09, 129.22, 128.55, 72.27, 71.73, 69.32, 69.23, 68.97, 28.63, 20.97. HRMS (ESI) calcd for C15H28O7Na [M + Na]+: 333.0950. Found: 333.0948. IR (KBr film) ν 3526, 3500, 3385, 3064, 2960, 2888, 1717, 1701, 1600, 1454, 1266, 1265, 1129, 1070, 813, 711 cm–1.

4.17. (−)-gala-Quercitol 2

Compound 16 (502.5 mg, 1.620 mmol) was dissolved in methanol (16 mL). Concentrated ammonia (4 mL) was added. The mixture was stirred at room temperature for 48 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 2:1), charcoal (1.0 g) was added, and the mixture was further stirred for 1 h. The mixture was filtered by suction, and the filtrate was concentrated to dryness by vacuum distillation to give the crude solid product. A mixed solvent of ether (20 mL) and pure water (15 mL) was added and stirred for 5 min. The two phases were separated, and the aqueous phase was washed twice with ether (2 × 15 mL). The aqueous solution was concentrated to dryness by vacuum distillation. Toluene (15 mL) was added and then removed by vacuum distillation. Toluene (15 mL) was added again and then removed again by vacuum distillation. Finally, (−)-gala-quercitol 2 (239.0 mg, 1.457 mmol) as off-white crystals was obtained in 90% yield (>99% purity). Mp 253–255 °C {lit.7 249–256 °C}. [α]D25 = −52.8 (c 1.0, H2O) {lit.7 [α]D = −53 (c 0.3, H2O)}. 1H NMR (400 MHz, D2O) δ 1.62 (ddd, J1 = 11.6 Hz, J2 = 11.2 Hz, J3 = 2.5 Hz, 1H, H-6α), 1.90 (ddd, J1 = 11.6 Hz, J2 = 4.5 Hz, J3 = 4.0 Hz, 1H, H-6β), 3.56–3.59 (m, 1H), 3.68–3.75 (m, 1H), 3.80–3.83 (m, 1H), 3.89–3.97 (m, 2H). 13C NMR (D2O) δ 73.10, 72.86, 72.65, 68.76, 67.26, 34.42. HRMS (ESI) calcd for C6H12O5Na [M + Na]+: 187.0582. Found: 187.0582. IR ν = 3313, 2937, 2900, 1420, 1074, 1063, 660 cm–1.

4.18. (1R,2S,3S,4S,5R)-1-Acetoxy-2-(tert-butyl-dimethylsilyloxy)-5-benzoyloxy-3,4-isopropylidenedioxy Cyclohexane 17

Compound 10 (501.5 mg, 1.187 mmol), triethylamine (240.0 mg, 2.372 mmol), and DMAP (30.0 mg, 0.245 mmol) were dissolved in ethyl acetate (5 mL). The solution was cooled to 0 °C by an ice bath. Acetic anhydride (158.0 mg, 1.548 mmol) was added dropwise, and the mixture was then stirred at 0 °C for 2 h. After the reaction was complete (checked by TLC, eluent: EtOAc/hexane = 1:4), ethyl acetate (30 mL) and an aqueous HCl solution (1 M, 5 mL) were added. The mixture was vigorously stirred for 5 min, and then the two phases were separated by a separatory funnel. The organic phase was washed successively with an aqueous solution of potassium carbonate (10% w/w, 10 mL) and brine (5 mL). After the organic solution was dried over anhydrous MgSO4, the solvent was removed by vacuum distillation to give the crude product, which was then purified by flash chromatography (eluent: EtOAc/hexane = 1:4) to afford compound 17 (529.0 mg, 1.139 mmol) as a colorless oil in 96% yield. [α]D25 = +16.8 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) δ 0.12 (s, 3H), 0.16 (s, 3H), 0.91 (s, 9H), 1.37 (s, 3H), 1.55 (s, 3H), 1.99–2.05 (m, 1H, H-6α), 2.07 (s, 3H, CH3 in Ac), 2.11–2.17 (m, 1H, H-6β), 3.96 (dd, J1 = 7.0 Hz, J2 = 5.3 Hz, 1H). 4.15 (dd, J1 = 5.5 Hz, J2 = 5.3 Hz, 1H), 4.29 (dd, J1 = 5.5 Hz, J2 = 5.6 Hz, 1H), 4.98–5.03 (m, 1H, H-1), 5.53–5.57 (m, 1H, H-5), 7.45 (dd, J1 = 7.8 Hz. J2 = 8.0 Hz, 2H), 7.57 (d, J = 7.8 Hz, 1H), 8.06 (d, J = 8.0 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 170.21, 165.56, 133.23, 129.79, 129.77, 128.42, 109.45, 80.00, 75.89, 72.68, 71.09, 69.79, 29.38, 28.03, 26.26, 25.71, 21.21, 18.02, −4.60, −4.83. HRMS (ESI) calcd for C24H36O7SiNa [M + Na]+: 487.2128. Found: 487.2129. IR (neat) ν 3067, 2933, 2857, 1743, 1723, 1603, 1452, 1369, 1275, 1235, 1109, 1095, 1024, 838, 777, 709 cm–1.

Acknowledgments

We are grateful to the National Natural Science Foundation of China (Nos. 20972048 and 20172015) for the financial support of this work.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.9b02986.

  • 1H and 13C NMR spectra of compounds 1–17 (PDF)

The authors declare no competing financial interest.

Dedication

Dedicated to Professor Li-Xin Dai of SIOC for the celebration of his 95th birthday.

Supplementary Material

ao9b02986_si_001.pdf (1.4MB, pdf)

References

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