ࡱ> 9 Rbjbj6>\ lffffL,H&lVVVV!!!EEEEEEE$J MFy!!!!F{(VVH{({({(!VVE{(!E{({( -jAhEV @b_8 f$D2E H0HD.0Nk(0NE{(Supporting Information Facile Synthetic Routes to All Possible Enantiomeric Pairs of Conduritol Stereoisomers via Efficient Enzymatic Resolution of Conduritol B and C Derivatives Yong-Uk Kwon and Sung-Kee Chung* Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science & Technology, Pohang 790-784, South Korea E-mail: skchung@postech.ac.kr (()-1,2,3/4)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [2]22 To a stirred solution of compound 120 (2.60 g, 6.07 mmol), imidazole (1.67 g, 24.5 mmol), and triphenylphosphine (6.49 g, 24.5 mmol) in toluene (120 mL) at reflux, was added iodine (5.08 g, 20.0 mmol) portionwise. The mixture was stirred for 5.5 h, cooled to rt, decanted into excess aq. sodium thiosulfate and aq. NaHCO3, and diluted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and concentrated. The product mixture was subjected to column chromatography to give compound 2 (1.84 g, 77%). Rf 0.25 (EtOAc : Hex = 1 : 10); mp 120.5-122 C; 1H NMR (CDCl3)  1.37, 1.43 (2s, 6H, CMe2), 4.68 (dd, J = 3.1, 7.4 Hz, 1H, H-2 or H-3), 4.83 (dd, J = 4.0, 7.4 Hz, 1H, H-3 or H-2), 5.69 (app. t, J = 3.3 Hz, 1H, H-1 or H-4), 5.86 (dd, J = 2.1, 4.0 Hz, 1H, H-4 or H-1), 6.18-6.26 (m, 2H, H-5 & H-6), 7.43-8.14 (m, 10H, 2Ph); 13C NMR (CDCl3)  25.05, 26.60 [CMe2], 68.22, 70.27, 74.44, 76.47 [C-1 ~ C-4], 110.54 [CMe2], 128.60-133.67 [C-5, C-6 & 2Ph], 166.04, 166.48 [2COPh]; Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 70.11; H, 5.72. (()-(1,2,3/4)-2,3-O-Isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [3] To a solution of compound 2 (9.75 g, 24.7 mmol) in MeOH (100 mL), was added sodium methoxide (300 mg, 5.5 mmol). After stirring under reflux for 3 h, the mixture was filtered through a short pad of silica gel and the filtrate was evaporated under reduced pressure. The crude product was subjected to column chromatography to give compound 3 (4.42 g, 96%) as a solid. Rf 0.12 (EtOAc : Hex = 1 : 2); mp 95-96 C; 1H NMR (CDCl3)  1.39, 1.46 (2s, 6H, CMe2), 2.37 (br. s, 1H, OH), 2.70 (d, J = 4.7 Hz, 1H, OH), 4.30-4.34 (m, 1H, H-2 or H-3), 4.44-4.47 (m, 2H, H-3 or H-2 & H-1 or H-4), 4.52 (br. s,1H, H-4 or H-1), 5.98-6.07 (m, 2H, H-5 & H-6); 13C NMR (CDCl3)  24.80, 26.72 [CMe2], 64.63, 68.47, 75.56, 79.42 [C-1 ~ C-4], 110.04 [CMe2], 132.16, 133.49 [C-5 & C-6]; Anal. Calcd for C9H14O4: C, 58.05; H, 7.58. Found: C, 57.86; H, 7.55. (()-(1,2,3/4)-1,4-Di-O-acetyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [4] To a solution of compound 3 (4.29 g, 23.0 mmol) in pyridine (80 mL) at 0 C, was added acetic anhydride (4.4 mL, 46.1 mmol). After 30 min, the mixture was warmed up to rt and stirred overnight. The reaction mixture was treated with water and extracted with EtOAc. The organic layer was washed with 1 N HCl, aq. NaHCO3, and brine. The organic layer was dried over MgSO4, concentrated and chromatographed to give 4 (6.07 g, 97.5%) as an oil. Rf 0.39 (EtOAc : Hex = 1 : 4); 1H NMR (CDCl3)  1.34, 1.41 (2s, 6H, CMe2), 2.05, 2.15 (2s, 6H, 2COCH3), 4.45 (dd, J = 2.3, 7.2 Hz, 1H, H-2 or H-3), 4.67 (ddd, J = 0.85, 3.9, 7.2 Hz, 1H, H-3 or H-2), 5.25 (dd, J = 2.3, 4.6 Hz, 1H, H-1 or H-4), 5.50-5.53 (m, 1H, H-4 or H-1), 5.98 (ddd, J = 0.85, 2.5, 9.8 Hz, 1H, H-5 or H-6), 6.06 (ddd, J = 1.4, 4.6, 9.8 Hz, 1H, H-6 or H-5); 13C NMR (CDCl3)  20.74, 20.90 [2COCH3], 24.48, 26.03 [CMe2], 67.46, 68.45, 73.99, 75.73 [C-1 ~ C-4], 109.69 [CMe2], 127.78, 131.75 [C-5 & C-6], 169.68, 170.25 [2COCH3]. Lipase-catalyzed Resolution of Compound 4 To a solution of racemate 4 (6.65 g, 24.6 mmol) in 0.5 N sodium phosphate buffer (120 mL, pH 7.0), was added lipase (ca. 2.5 g) from Candida rugosa (Sigma) or Pseudomonas cepacia. (Amano). This suspension was vigorously stirred with its pH automatically adjusted to 7.0 with 0.5 N NaOH. After 3 h, conversion was ca 50%, and EtOAc (40 mL) was added. The suspension was filtered through Celite and the mixture was extracted 3 times with EtOAc. The combined extracts were washed with aq. NaHCO3 and brine, dried (MgSO4), concentrated and chromatographed to give (+)-4 (3.26 g, 49%, 95% ee) as an oil, and (-)-5 (2.70 g, 48%, 95% ee) whose optical purity could be improved to >99% ee after recrystallization from CH2Cl2-Hex. The optical purity of (+)-4 could also be enhanced to >99% ee after repeated resolution. After acetylation of the monoacetate (-)-5, the optical purities (% ee) were determined by NMR analysis of the diacetates using europium tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorate] as the NMR shift agent. Compounds (+)-4 and (-)-5 were treated with NaOMe in MeOH to give compounds (+)-3 and (-)-3, and their optical purities again could be improved to >99% ee by recrystallization from CH2Cl2-MeOH. (+)-(1S,2R,3S,4S)-1,4-Di-O-acetyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-4] Identical Rf, 1H NMR and 13C NMR data to those of 4; [(]eq \o(\s\up 6(20),\s\do 2(D)) +161.0 (c 4.60, CHCl3) [lit.19c [(]eq \o(\s\up 6(20),\s\do 2(D)) +154.7 (c 1.106, CHCl3)]. ()-(1R,2R,3R,4R)-4-O-Acetyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [()-5] Rf 0.26 (EtOAc : Hex = 1 : 2); mp 63-64 C; [(]eq \o(\s\up 6(20),\s\do 2(D))  206.7 (c 4.23, CHCl3); 1H NMR (CDCl3)  1.37, 1.41 (2s, 6H, CMe2), 2.04 (s, 3H, COCH3), 3.07 (br. s, 1H, OH-1), 4.40-4.45 (m, 2H, H-1 & H-3), 4.59 (ddd, J = 1.0, 4.3, 7.3 Hz, 1H, H-2), 5.23 (dd, J = 2.8, 4.9 Hz, 1H, H-4), 5.97 (ddd, J = 1.4, 4.9, 9.8 Hz, 1H, H-5), 6.05 (ddd, J = 1.0, 2.5, 9.8 Hz, 1H, H-6); 13C NMR (CDCl3)  21.19 [COCH3], 24.84, 26.43 [CMe2], 65.41, 68.66, 75.92, 76.02 [C-1 ~ C-4], 109.72 [CMe2], 126.65, 136.53 [C-5 & C-6], 170.26 [COCH3]; Anal. Calcd for C11H16O5: C, 57.88; H, 7.07. Found: C, 57.65; H, 7.20. (+)-(1S,2S,3R,4S)- & ()-(1R,2R,3S,4R)-2,3-O-Isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-3 & ()-3] (+)-3: Identical Rf, 1H NMR and 13C NMR data to those of 3; mp 122-123 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +88.6 (c 1.11, CHCl3). ()-3: Identical Rf, 1H NMR and 13C NMR data to those of 3; mp 122-123 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 88.5 (c 1.00, CHCl3) [lit.19c [(]eq \o(\s\up 6(20),\s\do 2(D)) 157.2 (c 0.998, CHCl3)]. (()-(1,3/2,4)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [10] Compound 920 (6.98 g, 16.3 mmol) was treated by the same procedure as described for compound 2 to afford compound 10 (5.01 g, 78%). Rf 0.42 (EtOAc : Hex = 1 : 4); mp 193-194 C; 1H NMR (CDCl3)  1.51 (s, 6H, CMe2), 4.04 (dd, J = 2.4, 5.8 Hz, 2H, H-2 & H-3), 5.85-5.90 (m, 4H, H-1, H-4, H-5 & H-6), 7.26-8.11 (m, 10H, 2Ph); 13C NMR (CDCl3)  27.36 (2C) [CMe2], 73.26 (2C), 78.03 (2C) [C-1 ~ C-4], 112.39 [CMe2], 128.81-133.76 [C-5, C-6 & 2Ph], 166.36 (2C) [2COPh]; Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 70.22; H, 5.84. (()-(1,3/2,4)-2,3-O-Isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [11] Compound 10 (4.0 g, 12.4 mmol) was treated by the same procedure as described for compound 3 to afford compound 11 (1.84 g, 97.4%) as an oil. Rf 0.23 (EtOAc : Hex = 1 : 1); 1H NMR (CDCl3)  1.47 (s, 6H, CMe2), 2.74 (br. s, 2H, 2OH), 3.55 (dd, J = 2.3, 5.6 Hz, 2H, H-2 & H-3), 4.50 (dd, J = 2.3, 5.6 Hz, 2H, H-1 & H-4), 5.69 (s, 2H, H-5 & H-6); 13C NMR (CDCl3)  27.35 (2C) [CMe2], 71.08 (2C), 81.13 (2C) [C-1 ~ C-4], 111.71 [CMe2], 130.86 (2C) [C-5 & C-6]. (()-(1,3/2,4)-1,4-Di-O-acetyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [12] Compound 11 (3.25 g, 17.4 mmol) was treated by the same procedure as described for compound 4 to afford compound 12 (4.66 g, 98.8%) as a solid. Rf 0.5 (EtOAc : Hex = 1 : 2); mp 153-154 C; 1H NMR (CDCl3)  1.48 (s, 6H, CMe2), 2.13 (s, 6H, 2COCH3), 3.79 (dd, J = 2.4, 5.9 Hz, 2H, H-2 & H-3), 5.54 (dd, J = 2.4, 5.9 Hz, 2H, H-1 & H-4), 5.70 (s, 2H, H-5 & H-6); 13C NMR (CDCl3)  21.41 (2C) [2COCH3], 27.24 (2C) [CMe2], 72.70 (2C), 77.67 (2C) [C-1 ~ C-4], 112.22 [CMe2], 128.87 (2C) [C-5 & C-6], 170.72 (2C) [2COCH3]; Anal. Calcd for C13H18O6: C, 57,77; H, 6.71. Found: C, 57.39; H, 6.89. Lipase-catalyzed Resolution of Compound 12 To a solution of the racemate 12 (2.71 g, 10.0 mmol) and Novozym 435 (immobilized lipase from Candida Antarctica, Novo Nordisk, 3.0 g) in t-BME (150 mL), was added n-BuOH (9.3 mL). The reaction mixture was stirred at 45 C. After 30 min, the reaction mixture contained (+)-12, ()-13 and ()-11. The monoacetate ()-13 was slowly converted to ()-11. After 3 h, the enzyme was filtered off and the filtrate was concentrated and chromatographed to give the unreacted diacetate (+)-12 (1.34 g, 49.5%, 98% ee) whose optical purity could be improved to >99% ee by recrystallization from EtOAc-pet. ether, and the diol ()-11 (906 mg, 48.5%, >99% ee) as an oil. After acetylation of the diol ()-11, the optical purities (% ee) were determined by NMR analysis of the diacetates using europium tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorate] as the NMR shift agent. Compound (+)-12 was treated with NaOMe in MeOH to give the diol (+)-11. (+)-(1S,2S,3S,4S)-1,4-Di-O-acetyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-12] Identical Rf, 1H NMR and 13C NMR data to those of 12; mp 94-95 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +180.3 (c 1.27, CHCl3). ()-(1R,2R,3S,4R)-1-O-Acetyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [()-13] Rf 0.26 (EtOAc : Hex = 1 : 2); [(]eq \o(\s\up 6(20),\s\do 2(D)) 94.4 (c 1.98, CHCl3); 1H NMR (CDCl3)  1.48 (s, 6H, CMe2), 2.12 (s, 3H, COCH3), 2.94 (br. s, 1H, OH-4), 3.62 (dd, J = 8.0, 9.8 Hz, 1H, H-2 or H-3), 3.71 (dd, J = 8.4, 9.8 Hz, 1H, H-3 or H-2), 4.48-4.51 (m, 1H, H-4), 5.51-5.56 (m, 1H, H-1), 5.64 (td, J = 2.0, 2.0, 10.2 Hz, 1H, H-5 or H-6), 5.74 (td, J = 1.8, 1.8, 10.2 Hz, 1H, H-6 or H-5); 13C NMR (CDCl3)  21.50 [COCH3], 27.25, 27.35 [CMe2], 70.79, 73.24, 77.50, 81.22 [C-1 ~ C-4], 111.95 [CMe2], 127.04, 132.72 [C-5 & C-6], 170.98 [COCH3]. (+)-(1S,2R,3R,4S)- & ( )-(1R,2S,3S,4R)-2,3-O-Isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-11 & ()-11] (+)-11: Identical Rf, 1H NMR and 13C NMR data to those of 11; [(]eq \o(\s\up 6(20),\s\do 2(D)) +30.4 (c 3.98, CHCl3). ()-11: Identical Rf, 1H NMR and 13C NMR data to those of 11; [(]eq \o(\s\up 6(20),\s\do 2(D)) 30.2 (c 2.40, CHCl3). (+)-(1S,2R,3R,4S)- & ()-(1R,2S,3S,4R)-1-O-Benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-15 & ()-15], (+)-(1S,2S,3S,4S)- & ()-(1R,2R,3R,4R)-4-O-Benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-16 & ()-16], and (+)-(1S,2R,3S,4S)- & ()-(1R,2S,3R,4R)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-2 & ()-2] To a solution of compound (+)-3 (1.865 g, 10 mmol) in pyridine (50 mL) at 0 C, was added BzCl (1.2 mL, 10.2 mmol) dropwise. After stirring for 5 h at 0-10 C, the mixture was treated with water (3 mL) for 30 min, diluted with EtOAc, and washed with 1 N HCl, aq. NaHCO3, and brine. The organic layer was separated, dried (MgSO4), concentrated and chromatographed to afford (+)-2 (448 mg, 11.3%), (+)-15 (1.69 g, 58.3%), (+)-16 (211 mg, 7.3%), and the starting material (+)-3 (345 mg, 18.5%). (+)-2: Identical Rf, 1H NMR and 13C NMR data to those of 2; mp 140-141 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +175.3 (c 1.66, CHCl3). (+)-15: Rf 0.25 (EtOAc : Hex = 1 : 2); mp 128-129 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +190.5 (c 2.07, CHCl3); 1H NMR (CDCl3)  1.34, 1.36 (2s, 6H, CMe2), 2.77 (br. s, 1H, OH-4), 4.37 (dd, J = 4.3, 8.0 Hz, 1H, H-3), 4.53 (dd, J = 4.2, 8.0 Hz, 1H, H-2), 4.65 (br. s, 1H, H-4), 5.75 (app. t, J = 4.3 Hz, 1H, H-1), 6.06 (ddd, J = 1.4, 4.4, 9.4 Hz, 1H, H-6), 6.13 (dd, J = 2.8, 9.4 Hz, 1H, H-5), 7.37-8.04 (m, 5H, Ph); 13C NMR (CDCl3)  24.90, 26.67 [CMe2], 67.33, 69.71, 74.26, 79.85 [C-1 ~ C-4], 110.48 [CMe2], 127.84-136.39 [C-5, C-6 & Ph], 166.39 [COPh]; Anal. Calcd for C16H18O5: C, 66.19; H, 6.25. Found: C, 65.79; H, 6.28. (+)-16: Rf 0.32 (EtOAc : Hex = 1 : 2); mp 124-125 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +205.6 (c 1.04, CHCl3); 1H NMR (CDCl3)  1.39, 1.45 (2s, 6H, CMe2), 2.67 (br. s, 1H, OH-1), 4.50 (br. s, 1H, H-1), 4.61 (dd, J = 2.8, 7.3 Hz, 1H, H-3), 4.68 (dd, J = 4.4, 7.3 Hz, 1H, H-2), 5.53 (app. q, J = 2.7 Hz, 1H, H-4), 6.11 (m, 2H, H-5 & H-6), 7.41-8.00 (m, 5H, Ph); 13C NMR (CDCl3)  24.97, 26.55 [CMe2], 65.72, 68.98, 75.90, 75.96 [C-1 ~ C-4], 110.01 [CMe2], 126.92-136.84 [C-5, C-6 & Ph], 1165.89 [COPh]; Anal. Calcd for C16H18O5: C, 66.19; H, 6.25. Found: C, 65.89; H, 6.42. Similarly, compound ()-3 was converted to compounds ()-2, ()-15, ()-16, and the starting material ()-3. ()-2: Identical Rf, 1H NMR and 13C NMR data to those of 2; mp 140-141 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 175.3 (c 1.62, CHCl3). ()-15: Identical Rf, 1H NMR and 13C NMR data to those of (+)-15; mp 128-129 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 190.2 (c 2.15, CHCl3). ()-16: Identical Rf, 1H NMR and 13C NMR data to those of (+)-16; mp 124-125 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 205.5 (c 1.05 , CHCl3). (+)-(4S,5R,6S)- & ()-(4R,5S,6R)-4-Bezoyloxy-5,6-(isopropylidenedioxy)cyclohex-2-en-1-one [(+)-17 & ()-17] To a solution of compound (+)-15 (581 mg, 2 mmol) and TEA (3 mL, 21.4 mmol) in DMSO (6 mL) at 15 C, was added sulfer trioxide-pyridine complex (1.136 g, 7 mmol) in DMSO (4 mL). After slowly warmed up to rt and stirred for 3 h, the mixture was poured into cooled brine, and extracted with EtOAc three times. The organic extracts were washed with 0.1 N HCl and brine, dried (MgSO4) and concentrated to afford the enone (+)-17 which was used for the next step without further purification. (+)-17: Rf 0.41 (EtOAc : Hex = 1 : 2); 1H NMR (CDCl3)  1.38, 1.40 (2s, 6H, CMe2), 4.44 (d, J = 4.7 Hz, 1H, H-6), 4.91 (dt, J = 2.2, 4.4, 4.4 Hz, 1H, H-5), 6.16 (td, J = 2.4, 2.4, 4.1 Hz, 1H, H-4), 6.22 (dd, J = 2.5, 10.4 Hz, 1H, H-2), 6.90 (td, J = 2.2, 2.2, 10.4, 9.4 Hz, 1H, H-3), 7.45-8.15 (m, 5H, Ph); 13C NMR (CDCl3)  26.44, 27.78 [CMe2], 67.74, 74.91, 75.82 [C-4 ~ C-6], 111.60 [CMe2], 128.82-146.38 [C-2, C-3 & Ph], 166.14 [COPh], 195.56 [C-1]. Similarly, compound ()-17 was prepared from compound ()-15. ()-17: Identical Rf, 1H NMR and 13C NMR data to those of (+)-17. ()-(1S,2R,3R,4R)- & (+)-(1R,2S,3S,4S)-1-O-Benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [()-18 & (+)-18] To a solution of the crude enone (+)-17 in MeOH-CH2Cl2 (1 : 5, 12 mL) at 0 C, was added NaBH4 (193 mg, 5 mmol). After stirring at rt for 2.5 h, the mixture was treated with water (2 mL), evaporated, and diluted with EtOAc. The organic layer was washed with water and brine, dried (MgSO4), concentrated and chromatographed to afford compound ()-18 (433 mg, 74.5% from (+)-15). ()-18: Rf 0.24 (EtOAc : Hex = 1 : 2); mp 108-109 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 42.6 (c 1.03, CHCl3); 1H NMR (CDCl3)  1.35, 1.42 (2s, 6H, CMe2), 2.66 (br. s, 1H, OH-4), 4.10 (br. s, 1H, H-4), 4.60 (ddd, J = 1.6, 4.8, 7.4 Hz, 1H, H-3), 4.82 (ddd, J = 1.7, 3.7, 7.4 Hz, 1H, H-2), 5.33-5.36 (m, 1H, H-1), 5.76-5.81 (m, 1H, H-6), 5.83-5.88 (m, 1H, H-5), 7.44-8.14 (m, 5H, Ph); 13C NMR (CDCl3)  25.17, 26.13 [CMe2], 66.98, 69.95, 74.07, 75.65 [C-1 ~ C-4], 110.59 [CMe2], 126.67-133.71 [C-5, C-6 & Ph], 166.62 [COPh]; Anal. Calcd for C16H18O5: C, 66.19; H, 6.25. Found: C, 65.87; H, 6.34. Similarly, compound (+)-18 was prepared from compound ()-15 via compound ()-17. (+)-18: Identical Rf, 1H NMR and 13C NMR data to those of ()-18; mp 108-109 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +42.5 (c 0.74, CHCl3). (+)-(1S,2S,3R,4S)- & ()-(1R,2R,3S,4R)-2,3-O-Isopropylidene-4-O-methoxymethylcyclohex-5-ene-1,2,3,4-tetrol [(+)-20 & ()-20] To a solution of compound (+)-15 (900 mg, 3.10 mmol) in chloroform (12 mL), were added N,N-diisopropylethylamine (2.2 mL, 12.6 mmol) and chloromethyl methyl ether (0.71 mL, 9.35 mmol). After stirring at rt overnight, the reaction mixture was diluted with CH2Cl2. The organic layer was washed with aq. NaHCO3 and brine, dried, and concentrated to dryness. The crude mixture was treated with 25 wt% sodium methoxide (in MeOH, 0.2 mL) in MeOH (12 mL). After refluxing for 3 h, the mixture was filtered through a short pad of silica gel and the filtrate was evaporated under reduced pressure. Column chromatography gave compound (+)-20 (693 mg, 97.1%) as an oil. (+)-20: Rf 0.22 (EtOAc : Hex = 1 : 2); [(]eq \o(\s\up 6(20),\s\do 2(D)) +111.3 (c 1.21, CHCl3); 1H NMR (CDCl3)  1.37, 1.41 (2s, 6H, CMe2), 2.99 (br. s, 1H, OH-1), 3.36 (s, 3H, CH2OCH3), 4.29 (app. t, J = 3.4 Hz, 1H, H-1 or H-4), 4.38-4.44 (m, 2H, H-4 or H-1 & H-2 or H-3), 4.51 (dd, J = 4.1, 7.5 Hz, 1H, H-3 or H-2), 4.65 (d, J = 6.7 Hz, 1H, CHaHbOCH3), 4.68 (d, J = 6.7 Hz, 1H, CHaHbOCH3), 5.97-6.03 (m, 2H, H-5 & H-6); 13C NMR (CDCl3)  24.77, 26.50 [CMe2], 55.68 [CH2OCH3], 65.29, 71.37, 76.11, 77.45 [C-1 ~ C-4], 95.34 [CH2OCH3], 109.48 [CMe2], 129.44, 134.65 [C-5 & C-6]. Similarly, compound ()-20 was prepared from ()-15. ()-20: Identical Rf, 1H NMR and 13C NMR data to those of (+)-20; [(]eq \o(\s\up 6(20),\s\do 2(D)) 111.5 (c 2.25, CHCl3). ()-(1R,2R,3R,4S)- & (+)-(1S,2S,3S,4R)-1-O-Benzoyl-2,3-O-isopropylidene-4-O-methoxymethylcyclohex-5-ene-1,2,3,4-tetrol [()-21 & (+)-21] Compound (+)-20 (665 mg, 2.89 mmol) was treated by the same procedure as described for the Mitsunobu reaction of compound 15 to give compound ()-21 (938 mg, 97.1%) as an oil. ()-21: Rf 0.55 (EtOAc : Hex = 1 : 4); [(]eq \o(\s\up 6(20),\s\do 2(D))  91.7 (c 4.37, CHCl3); 1H NMR (CDCl3)  1.39, 1.51 (2s, 6H, CMe2), 3.34 (s, 3H, CH2OCH3), 4.26-4.31 (m, 2H, H-3 & H-4), 4.39-4.44 (m, 1H, H-2), 4.79 (d, J = 6.7 Hz, 1H, CHaHbOCH3), 4.90 (d, J = 6.7 Hz, 1H, CHaHbOCH3), 5.47-5.51 (m, 1H, H-1), 5.78 (td, J = 2.1, 2.1, 10.0 Hz, 1H, H-5), 5.91 (td, J = 2.2, 2.2, 10.0 Hz, 1H, H-6), 7.42-8.11 (m, 5H, Ph); 13C NMR (CDCl3)  25.46, 27.59 [CMe2], 55.96 [CH2OCH3], 73.27, 74.94, 76.41, 77.87 [C-1 ~ C-4], 96.21 [CH2OCH3], 109.97 [CMe2], 127.95-133.60 [C-5, C-6 & Ph], 166.32 [COPh]. Similarly, compound (+)-21 was prepared from compound ()-20. (+)-21: Identical Rf, 1H NMR and 13C NMR data to those of ()-21; [(]eq \o(\s\up 6(20),\s\do 2(D)) +91.3 (c 4.16, CHCl3). (1,2,3,4)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [25] and (()-(1,2,3/4)-3,4-Di-O-benzoyl-1,2-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [26] To a solution of the racemate 15 (mp 132-133 C, 790 mg, 2.72 mmol), which was prepared from the racemate 3 by the same procedure as described for compound (+)-15, Ph3P (1.80 g, 6.79 mmol), and benzoic acid (839 mg, 6.79 mmol) in toluene (25 mL), was added dropwise diethyl azodicarboxylate (1.1 mL, 6.79 mmol). After stirring at rt for 3 h, the mixture was filtered through silica gel (EtOAc-Hex = 1 : 4), concentrated and chromatographed to afford compounds 25 (91 mg, 8.5%) and 26 (785 mg, 73.1 %). 25: Rf 0.6 (EtOAc : Hex = 1 : 2); mp 201-202 C; 1H NMR (CDCl3)  1.33, 1.44 (2s, 6H, CMe2), 4.88 (app. t, J = 1.2 Hz, 2H, H-2 & H-3), 5.42 (dd, J = 2.4 Hz, 2H, H-1 & H-4), 5.96 (s, 2H, H-5 & H-6), 7.45-8.16 (m, 10H, 2Ph); 13C NMR (CDCl3)  24.94, 25.93 [CMe2], 69.78 (2C), 73.85 (2C) [C-1 ~ C-4], 110.68 [CMe2], 127.58-133.48 [C-5, C-6 & Ph], 166.33 (2C) [2COPh]; Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 69.83; H, 5.66. 26: Rf 0.61 (EtOAc : Hex = 1 : 2); mp 108-110 C; 1H NMR (CDCl3)  1.36, 1.45 (2s, 6H, CMe2), 4.71 (dd, J = 2.3, 8.4 Hz, 1H, H-2), 4.78-4.80 (m, 1H, H-1), 5.58 (dd, J = 2.3, 8.9 Hz, 1H, H-3), 5.83 (m, 2H, H-5 & H-6), 6.13 (br. d, J = 8.9 Hz, 1H, H-4), 7.33-8.06 (m, 10H, 2Ph); 13C NMR (CDCl3)  27.18, 28.20 [CMe2], 69.43, 72.84, 74.03, 74.91 [C-1 ~ C-4], 111.05 [CMe2], 127.18-133.71 [C-5, C-6 & Ph], 166.42, 166.59 [2COPh]; Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 69.79; H, 5.84. ()-(1R,2S,3S,4R)- & (+)-(1S,2R,3R,4S)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [()-27 & (+)-27] To a solution of compound (+)-11 (295 mg, 1.58 mmol), Ph3P (2.91 g, 11.0 mmol), and benzoic acid (1.35 g, 10.9 mmol) in toluene (20 mL), was added dropwise diethyl azodicarboxylate (1.9 mL, 11.7 mmol). After stirring at rt for 6 h, the mixture was filtered through silica gel (EtOAc-Hex = 1 : 2), concentrated and chromatographed to afford compound (-)-27 (562 mg, 90%) as a solid. ( )-27: Rf 0.59 (EtOAc : Hex = 1 : 2); mp 119-120 C; [(]eq \o(\s\up 6(20),\s\do 2(D))  452.3 (c 1.17, CHCl3); 1H NMR (CDCl3)  1.41 (s, 6H, CMe2), 4.33 (d, J = 1.1 Hz, 2H, H-2 & H-3), 5.96 (d, J = 1.1 Hz, 2H, H-1 & H-4), 6.26 (m, 2H, H-5 & H-6), 7.43-8.07 (m, 10H, 2Ph); 13C NMR (CDCl3)  27.10 (2C) [CMe2], 66.73 (2C), 72.90 (2C) [C-1 ~ C-4], 111.54 [CMe2], 126.29-133.63 [C-5, C-6 & Ph], 166.25 (2C) [2COPh]; Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 69.74; H, 5.73. Similarly, compound (+)-27 was prepared from compound ()-11. (+)-27: Identical Rf, 1H NMR and 13C NMR data to those of ()-27; mp 119-120 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +453.2 (c 1.24, CHCl3). (+)-(1S,2S,3R,4S)- & ()-(1R,2R,3S,4R)-1-O-Benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-29 & ()-29] and (+)-(1S,2S,3S,4S)- & ()-(1R,2R,3R,4R)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [(+)-10 & ()-10] To the solution of (+)-11 (620 mg, 3.3 mmol) in pyridine (15 mL) at 0 C, was added BzCl (0.41 mL, 3.50 mmol) dropwise. After stirring at 0-5 C for 5 h, the mixture was treated with water (2 mL) for 20 min, diluted with EtOAc, and washed with 1 N HCl, aq. NaHCO3, and brine. The organic layer was separated, dried (MgSO4), concentrated and chromatographed to afford the dibenzoate (+)-10 (184 mg, 14%), the monobenzoate (+)-29 (590 mg, 61%), and the starting material (+)-11 (58 mg, 9.4 %). (+)-10: Identical Rf, 1H NMR and 13C NMR data to those of 10; mp 182-184 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +208.2 (c 1.12, CHCl3). (+)-29: Rf 0.27 (EtOAc : Hex = 1 : 2); mp 123-124 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) +172.1 (c 1.71, CHCl3); 1H NMR (CDCl3)  1.50 (s, 6H, CMe2), 3.46 (br. s, 1H, OH-4), 3.71 (dd, J = 8.3, 9.8 Hz, 1H, H-3), 3.88 (app. t, J = 9.2 Hz, 1H, H-2), 4.55 (br. d, J = 7.1Hz, 1H, H-4), 5.71-5.83 (m, 3H, H-1, H-5 & H-6), 7.41-8.09 (m, 5H, Ph); 13C NMR (CDCl3)  27.31, 27.42 [CMe2], 70.89, 73.74, 77.76, 81.34 [C-1 ~ C-4], 112.02 [CMe2], 127.19, 128.77, 130.09, 130.25, 132.91, 133.69 [C-5, C-6 & Ph], 166.43 [COPh]; Anal. Calcd for C16H18O5: C, 66.19; H, 6.15. Found: C, 65.94; H, 6.54. Similarly, compound ()-11 was converted to the dibenzoate ()-10, the monobenzoate ()-29 and the starting material ()-11. ()-10: Identical Rf, 1H NMR and 13C NMR data to those of 10; mp 182-184 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 207.8 (c 1.13, CHCl3). ()-29: Identical Rf, 1H NMR and 13C NMR data to those of (+)-29; mp 123-124 C; [(]eq \o(\s\up 6(20),\s\do 2(D)) 172.9 (c 1.41, CHCl3). ()-(1R,2S,3S,4S)- & (+)-(1S,2R,3R,4R)-1,4-Di-O-benzoyl-2,3-O-isopropylidenecyclohex-5-ene-1,2,3,4-tetrol [()-30 & (+)-30] Compound (+)-29 (420 mg, 1.45 mmol) was treated by the same procedure as described for the Mitsunobu reaction of compound 15 to give compound ()-30 (560 mg, 98%) as an oil. ()-30: Rf 0.55 (EtOAc : Hex = 1 : 2); [(]eq \o(\s\up 6(20),\s\do 2(D)) 56.3 (c 3.29, CHCl3); 1H NMR (CDCl3)  1.43, 1.50 (2s, 6H, CMe2), 3.86 (dd, J = 3.7, 10.0 Hz, 1H, H-2 or H-3), 4.39 (dd, J = 8.9, 10.0 Hz, 1H, H-3 & H-2), 5.79 (br. d, J = 9.1 Hz, 1H, H-4 or H-1), 5.93 (app. t, J = 4.3 Hz, 1H, H-1 or H-4), 6.00 (dd, J = 1.8, 10.0 Hz, 1H, H-5 or H-6), 6.13 (ddd, J = 1.8, 5.0, 10.0 Hz, 1H, H-6 or H-5), 7.44-8.13 (m, 10H, 2Ph); 13C NMR (CDCl3)  27.02, 27.43 [CMe2], 66.35, 73.74, 74.57, 75.74 [C-1 ~ C-4], 111.96 [CMe2], 126.58-133.74 [C-5, C-6 & Ph], 166.16, 166.31 [2COPh]. Similarly, compound (+)-30 was prepared from ()-29. 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