Studies on Glycosides XVI. The Use of Mannosyl Trichloroacetate in the Synthesis of α-Mannosides and Related Oligosaccharides

Abstract

Much attention has been focused on the stereoselective synthesis of glycosides and oligosaccharides, not only for the preparation of natural products,¹ but also for the homologation of sugars to serve as chiral templates for more complex synthetic targets.² Most current methods for the preparation of glycosides are based on the activation of a leaving group at the anomeric centre.³ A wide range of (potential) leaving groups has been proposed. Some of them are stable in the absence of a suitable promoter and function as a temporary protecting group; others are very reactive.³ The trifluoroacetoxyl group was found to be a good leaving group at the anomeric position and C, O, S and N-glycosides,⁴ and oligosaccharides⁵ were synthesized with high stereoselectivity in our laboratory using derivatives that contain this group. However the glycosyl trifluoroacetates were found to be too reactive, and new glycosyl donors containing the trichloroacetoxy leaving group were studied. We now report a stereoselective and mild method for the synthesis of α-mannosides and related oligosaccharides from benzylated mannopyranosyl trichloroacetate (1).

Notes

Treatment of compound 1 with isopropyl alcohol at 40°C for 3h gave an α,β mixture (Yield 77%, α: β 1.2:1).

α-anomer: white solid, 59–60°C, [α]_D 31.85° (c 1.51, CHCl₃), δ_H1 = 5.00 ppm (J=1.97 Hz), δ_ci = 95.8 ppm. Anal. Calcd for C₃₇H₄₂O₆: C, 76.26; H, 7.26. Found: C, 76.24; H, 7.31.

β-anomer: white needles, 45–46.5°C, [α]_D -52.27° (c 1.70, CHCl₃), δ_H1 = 4.86 ppm (J=1.08 Hz), δ_c1 = 95.9 ppm. Anal. Calcd for C₃₇H₄₂O₆: C, 76.26; H, 7.26. Found: C, 76.29; H, 7.35.

Compound 1 was prepared as follows: To a solutioo of 2,3,4,6-tetra-O-benzyl-D-manoopyranose (1.08 g) in anhydrous dichloromethane (10 mL) were added tri-chloroacetyl anhydride (1.5 mL) and anhydrous sodium trichloroacetate (200 mg). The solution was boiled under reflux for 30 min. After cooling to it, the sodium trichloroacetate was filtered off, washed with CH₂Cl₂ (2x5 mL), the filtrate ane washings were combined and washed by ice-water, aqueous NaHCO₃ and ice-water to neutrality, dried, and concentrated under reduced pressure to give a colorless sysup, 1.37 g (quantitative yield). ¹H NMR (90 MHz, CDCl₃) δ (ppm): 3.60–5.10 (m, 14H, H-2,3,4,5,6, 4xPhCH₂), 6.36 (d, 1H, J=2.20Hz, H-1,α), 7.20–7.60 (m, 20H, ArH). ¹³C NMR chemical shifts are listed in Table 2. Anal. Calcd for C₃₆H₃₅O₇Cl₃: C, 63.14; H, 5.16; Cl, 15.33. Found: C, 63.03; H, 5.30; Cl, 15.32.

Selected ²J_C1-H1 data (Hz, measured by broadening band decoupling technique): 6: 173.0 (α); 7: 171.6 (α); 8: 171.7 (α); 9: 171.6 (α); 12: 168.5 (α); 13:170.3 (α); 15: 169.6 (α).

FAB-MS for selected compounds: 2: 644 (M⁺); 4: 658 (M⁺); 6: 610 (M⁺); 9: 647 (M+1)⁺; 11: 695 (M⁺); 13: 712 (M⁺); 14: 757 (M+Na)⁺; 15: 987 (M+1)⁺; 16: 934 (M⁺); 17: 724 (M⁺).

Elemental analysis: 2: Anal/ Calcd for C₄₁H₄₀O₇: C, 76.38; H, 6.25. Found: C, 76.32; H, 6.34. 3: Anal. Calcd for C₄₅H₄₂O₇: C, 77.78; H, 6.10. Found: C, 77.77; H, 6.00. 4: Anal. Calcd for C₄₂H₄₂O₇: C, 76.57; H, 6.43. Found: C, 76.70; H, 6.50. 5: Anal. Calcd for C₃₆H₃₇O₇Br: C, 65.36; H, 5.64; Br, 12.08. Found: C, 65.31; H, 5.70; Br, 12.02. 6: Anal. Calcd for C₃₈H₄₂O₇: C, 74.73; H, 6.93. Found: C, 74.80; H, 7.00. 7: Anal. Calcd for C₄₁H₃₉O₉N: C, 71.39; H, 5.70; N, 2.03. Found: C, 71.20; H, 5.70; N, 2.05. 8: Anal. Calcd for C₄₁H₄₀O₇: C, 76.38; H, 6.25. Found: C, 76.35; H, 6.30. 9: Anal. Calcd for C₄₁H₄₂O₅S: C, 76.13; H, 6.54. Found: C, 76.14; H, 6.50. 10: Anal. Calcd for C₄₀H₃₉O₈N: C, 72.60; H, 5.94; N, 2.12. Found: C, 72.71; H, 5.91; N, 2.11. 11: Anal. Calcd for C₄₀H₃₉O₆Br: C, 69.09; H, 5.65; Br, 11.49. Found: C, 69.00; H, 5.72;Br, 11.50. 12: Anal. Calcd for C₅₀H₆₈O₆: C, 78.49; H, 8.96. Found: C, 78.23; H, 8.95. 13: Anal. Calcd for C₄₅H₄₄O₈: C, 75.82; H, 6.22. Found: C, 75.90; H, 6.23. 14: Anal. Calcd for C₄₅H₄₄O₈: C, 75.82; H, 6.86. Found: C, 73.56; H, 6.92. 15: Anal. Calcd for C₆₂H₆₆O₁₁: C, 75.43; H, 6.74. Found: C, 75.13; H, 6.91. 16: Anal/ Calcd for C₅₇H₅₈O₁₂: C, 73.22; H, 6.25. Found: C, 73.21; H, 6.25. 17: Anal. Calcd for C₄₃H₄₈O₁₀: C, 71.25; H, 6.67. Found: C, 71.05; H, 6.50.