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Letters in Organic Chemistry
Volumn 4, Issue 2, 2007, Pages 142-145
Synthesis of alkyl β-D-Glcp-(1←3)-[β-D-Glcp- (1←6)]β-D-Glcp-(1←6)-β-D-Glucopyranosides with anti-tumor activity
Author keywords

Anti tumor; Carbohydrate; Glycosylation; Oligosaccharide; Synthesis; Trichloroacetimidate
Indexed keywords

EID: 34247585171     PISSN: 15701786     EISSN: None     Source Type: Journal    
DOI: 10.2174/157017807780414172     Document Type: Article
Times cited : (1)
References (22)
  • 11
    • 34247622272 scopus 로고    scopus 로고
    • All new compounds involved in this study were identified by optical rotations, 1H NMR or/and 13C NMR spectroscopy, and elemental analyses or ESIMS. Physical data and preparations for compound 4: A mixture of D-glucose (1, 9 g, 50 mmol) and chlorotripenylmethane (trityl chloride, 16.7 g, 60 mmol) in pyridine (80 mL) was stirred vigorously for 48 h at rt, at the end of which time TLC (3:1 petroleum ether-EtOAc) indicated that the reaction was complete. The mixture was cooled to 0 °C, then BzCl (26 mL, 220 mmol) was added dropwise within 30 min, then the reaction temperature was allowed to rise to rt. The mixture was stirred for 24 h. Water (200 mL) was added to the mixture, and stirring was continued for 30 min. The mixture was extracted with CH2Cl2, and the combined extracts were washed with N HCl and satd aq NaHCO3, dried Na2SO4, and concentrated to a syrup that was subjected to column chromatogr
    • 10: C, 54.84; H, 3.86. Found: C, 54.66; H, 3.98.
  • 12
    • 34247603441 scopus 로고    scopus 로고
    • Representative Procedure for Preparation of 5a-5b, TMSOTf (50 μL) was added to a solution of 4 (3.4 g, 5.0 mmol) and alcohol (6.0 mmol) in CH2Cl2 (50 mL) at rt. The reaction mixture was stirred for 2 h, at the end of which time TLC (5:1 petroleum ether-EtOAc) indicated that the reaction was complete. Then the mixture was neutralized with Et3N and concentrated to a residue under reduced pressure. The resulting residue was dissolved in a solution of 80 mL aq CH2Cl2-MeOH (v/v 2:1) containing 0.5% HCl at rt for 12 h, at the end of which time TLC (3:1 petroleum ether-EtOAc) indicated the reaction was complete. The solution was neutralized with Et3N and concentrated. The resultant residue was subjected to the column chromatography with 6:1 petroleum ether-EtOAc as eluent gave the target saccharide derivatives 5a-b as syrup 71-79% for two steps, Physical data for compound 5a: [α]D
    • 9: C, 69.52; H, 6.67. Found: C, 69.36; H, 6.88.
  • 13
    • 34247601040 scopus 로고    scopus 로고
    • Physical data for compound 5b: [α]D -9.8 (c 1.0, CHCl3, 1H NMR(400 MHz,CDCl3, δ 7.97-7.27(m, 15H, BzH, 5.93(t, 1H, J=9.8 Hz, 5.52-5.46(m, 2H, 4.82(d, 1H, J=7.6 Hz, H-1, 3.94(m, 1H, 3.86(dd, 1H, J=2.0, 12.4 Hz, 3.81-3.73(m, 2H, 3.53(m, 1H, 1.52-1.05(m, 20H, CH2C10H20CH3, 0.88(t, 3H, J=7.2 Hz, CH2CH3, 13C NMR(100 MHz, CDCl3, δ 166.14, 166.04, 165.88(3C, C(=O)Ph, 133.08-128.64(Ph, 104.14(1C, C-1, 76.34, 72.78, 71.44, 70.89, 68.08, 64.88(6C, C-2,3,4,5,6, OCH2, 31.85, 30.44, 29.41, 29.38, 29.24, 29.20, 29.17, 29.14, 25.64, 22.84, 14.1311C, OCH2C10H20CH3, Anal. Calcd for C39H48O9: C, 70.89; H, 7.32. Found: C, 70.58; H, 7.61
    • 9: C, 70.89; H, 7.32. Found: C, 70.58; H, 7.61.
  • 14
    • 34247621288 scopus 로고    scopus 로고
    • Physical data for compound 5c: [α]D -2.0 (c 1.0, CHCl3, 1H NMR(400 MHz,CDCl3, 7.99-7.27(m, 15H, BzH, 5.93(t, 1H, J=9.8 Hz, 5.52-5.43(m, 2H, 4.81(d, 1H, J=8.0 Hz, H-1, 3.94(m, 1H, 3.86(dd, 1H, J=2.0, 12.4 Hz, 3.81-3.73(m, 2H, 3.53(m, 1H, 1.54-1.06(m, 28H, CH2C14H28CH3, 0.88(t, 3H, J=7.0 Hz, CH2CH3, 13C NMR(100 MHz, CDCl3, δ 166.10, 165.91, 165.68(3C, C(=O)Ph, 133.11-128.46(Ph, 103.84(1C, C-1) 76.18, 72.97, 72.04, 71.189 67.66, 65.91(6C, C-2,3,4,5,6, OCH2, 31.77, 30.18, 29.44, 29.38, 29.34, 29.30, 29.28, 29.26, 29.24, 29.21, 29.18, 29.12, 26.01, 22.66, 14.1115C, OCH2C14H28 CH3, Anal. Calcd for C43 H56O9: C, 72.04; H, 7.87. Found: C, 71.86; H, 7.98
    • 9: C, 72.04; H, 7.87. Found: C, 71.86; H, 7.98.
  • 16
    • 34247633020 scopus 로고    scopus 로고
    • Representative Procedure for Preparation of 7a-7b. TMSOTf (30 μL) was added to a stirred solution of 5 (3.3 mmol) and 6 (4.7 g, 3.0 mmol) in dry CH2Cl2 (80 mL) at rt. The reaction mixture was stirred for 2 h, at the end of which time TLC (3:1 petroleum ether-EtOAc) indicated that the reaction was complete. Then the mixture was neutralized with Et3N and concentrated to a residue under reduced pressure. The residue was passed through a silicagel column with 3:1 petroleum ether-EtOAc as eluent to give the target saccharide derivatives 7a-b as syrup (71-79, Physical data for compound 7a: [α]D -6.2 (c 1.0, CHCl3, 1H NMR(400 MHz,CDCl3, δ 8.11-7.21 (m, 55H, BzH, 6.15(t, 1H, J=9.6 Hz, 5.96-5.85(m, 2H, 5.77-5.63(m, 2H, 5.61-5.52(m, 3H, 5.43(m, 1H, 5.10(d, 1H, J=8.0 Hz, 4.92(d, 1H, J=8.0 Hz, 4.77d, 1H, J=8.0 Hz, 4.71-4.51
    • 34: C, 67.59; H, 5.32. Found: C, 67.28; H, 5.60.
  • 17
    • 34247576200 scopus 로고    scopus 로고
    • Physical data for compound 7b: [α]D -15.2 (c 1.0, CHCl3, 1H NMR(400 MHz, CDCl3, δ 8.13-7.15 (m, 55H, BzH, 6.07(t, 1H, J=9.6 Hz, 5.88-5.77 (m, 2H, 5.69-5.59(m, 2H, 5.55-5.44(m, 3H, 5.35(m, 1H, 5.01(d, 1H, J=8.0 Hz, 4.83(d, 1H, J=8.0 Hz, 4.68(d, 1H, J=8.0 Hz, 4.63-4.55(m, 3H),4.50-4.43(m, 3H, 4.28(m, 1H, 4.09-4.05(m, 2H, 3.90-3.84(m, 2H, 3.81-3.67(m, 3H, 3.59(m, 1H, 3.47(m, 1H, 3.39-3.35(m, 2H, 1.94(s, 3H, COCH3, 1.89(s, 3H, COCH3, 1.49-0.99(m, 20H, CH2C10H20CH3, 0.88(t, 3H, J=7.2 Hz, CH2CH3, 13C NMR(100 MHz, CDCl3, δ 169.40, 168.07(2C, C(=O)CH3, 166.11,166.04,165.89,165.79, 165.72,165.39, 165.31, 165.16,165.11,165.03,165.00 (11C, C(=O)Ph, 133.63,128.18Ph, 101.21, 101.10, 100.94, 100
    • 34: C, 68.08; H,5.57. Found: C, 67.79.; H, 5.78.
  • 18
    • 34247616002 scopus 로고    scopus 로고
    • Physical data for compound 7c [α]D -17.5 (c 1.0, CHCl3, 1H NMR(400 MHz, CDCl3, δ 8.12-7.18 (m, 55H, BzH, 6.02(t, 1H, J=9.6 Hz, 5.79-5.67 (m, 2H, 5.62- 5.50(m, 2H, 5.46-5.33(m, 3H, 5.27(m, 1H, 5.00(d, 1H, J=8.0 Hz, 4.75(d, 1H, J=8.0 Hz, 4.57(d, 1H, J=8.0 Hz, 4.56-4.48(m, 3H),4.38-4.34(m, 3H, 4.21(m, 1H, 4.02-4.01(m, 2H, 3.82-3.75(m, 2H, 3.68-3.58(m, 3H, 3.49(m, 1H, 3.38(m, 1H, 3.30-3.26(m, 2H, 1.87(s, 3H, COCH3, 1.81(s, 3H, COCH3, 1.43-0.87(m, 28H, CH2C14H28CH3, 0.85(t, 3H, J=7.0 Hz, CH2CH3, 13C NMR(100 MHz, CDCl3, δ 169.36, 168.03(2C, C(=O)CH3, 166.08,166.00,165.94,165.82, 165.77,165.45, 165.34, 165.21,165.16,165.06,165.02 (11C, C(=O)Ph, 133.68,128.23(Ph, 101.16, 101.04, 100.86, 100.234C, C-1A
    • 34: C, 68.54; H,5.80. Found: C, 68.29; H, 5.97.
  • 19
    • 34247562244 scopus 로고    scopus 로고
    • Representative Procedure for Preparation of 8a-8b. Compound 7 was dissolved in a satd solution of NH3 in CH2Cl2 (30 mL) and MeOH (300 mL) at rt. After 96 h, the reaction mixture was concentrated, and the residue was washed four times with CH2Cl2 to afford the target saccharide derivatives 8a-b as amorphous white solid. Physical data for compound 8a: [α]D -16.0 (c 1.0, H2O, 1H NMR(400 MHz, D2O, 4.52-4.40(m, 3H, 4.17-4.12(m, 2H, 3.87-3.78(m, 5H, 3.71-3.52(m, 8H, 3.49-3.05(m, 12H),1.63-1.10(m, 12H, CH2C6H12CH3, 0.80(t, 3H, J=6.8 Hz, CH2CH3, 13C NMR(100 MHz, D2O, δ 103.35, 103.23, 103.06, 102.644C, C-1 A, 1B, 1C, 1D, Anal. Calcd for C32H58O21: C, 49.35; H, 7.5
    • +.
  • 20
    • 34247575189 scopus 로고    scopus 로고
    • Physical data for compound 8b: [α]D: -32.2 (c 1.0,H2O, 1H NMR (400MHz, D2O):4.62-4.55(m,4H, 4.54-4.51(m,3H, 4.31-3.95(m,2H, 3.80-3.62(m,4H, 3.61-3.48(m,3H, 3.47-3.10(m,14M, 1.43-0.97 (m,20H,C H2C10H2 0 CH3, 0.70(t,3H, J=5.6 Hz,C H2CH3, 13C NMR(100 MHz, D2O, δ 103.48, 103.35, 103.16, 102.79(4C, C-1A, 1B, 1C, 1D, Anal. Calcd for C36 H66 O21: C, 51.79; H, 7.97. Found: C, 51.87; H, 7.86. ESIMS for C36 H66 O21 834.91, 833.89[M-1
    • +.
  • 21
    • 34247624549 scopus 로고    scopus 로고
    • Physical data for compound 8c: [α]D: -34.5 (c 1.0,H2O, 1H NMR (400MHz, D2O, 13C NMR(100 MHz, D2O, δ 102.69, 102.54, 102.43, 101.96(4C, C-1A, 1B, 1C, 1D, Anal. Calcd for C40 H74 O21: C, 53.92;H, 8.37. Found: C, 53.53; H, 8.64. ESIMS for C40 H74 O21 891.01, 890.00[M-1
    • +.
  • 22
    • 34247569908 scopus 로고    scopus 로고
    • Bioassay for inhibition of S180: Cyclophosphamide was purchased from Shanghai Hualian Pharmaceutical Co. Ltd, No.030907, 120 female and male mice (weight 18-22 g, grade SPF) were obtained from Chongqing Academy of Chinese Materia Medica. The S180 cell line was provided by the Department of Tumorology, Institute of Pharmacy, the Chinese Academy of Medicines. The mice were randomly divided into 11 groups according to weight, and the S180 cell line of ascites cancer 0.2 mL (amount of cell 2×106) was planted intraperitoneally into the euterocelia. At 24 h after the planting, the mice were treated with the synthetic oligosacchrides or cyclophosphamide. The oligosaccharide 8a, 8b, 8c were dissolved in saline at 0.1 mg/mL, given with a dose of 1, 2, or 4 mg/kg/day to the mice within 10 consecutive days respectively. Cyclophosphamide was dissolved in saline at 4 mg/mL and administered intraperitoneally to the mice at a dose of 40 mg/kg each 2 day
    • 6) was planted intraperitoneally into the euterocelia. At 24 h after the planting, the mice were treated with the synthetic oligosacchrides or cyclophosphamide. The oligosaccharide 8a, 8b, 8c were dissolved in saline at 0.1 mg/mL, given with a dose of 1, 2, or 4 mg/kg/day to the mice within 10 consecutive days respectively. Cyclophosphamide was dissolved in saline at 4 mg/mL and administered intraperitoneally to the mice at a dose of 40 mg/kg each 2 days over 10 consecutive days.

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