Glycosylation with 2′-Carboxybenzyl Glycosides as Glycosyl Donors: Scope and Application to the Synthesis of a Tetrasaccharide

Abstract

Glycosylation of 2′-carboxybenzyl (CB) 2,3,4,6-tetra-O-benzyl-α-d-mannopyranoside (3), CB 2,3,4,6-tetra-O-benzyl-β-d-glucopyranoside (4), and CB 2,3-di-O-benzyl-4,6-O-benzylidene-β-d-glucopyranoside (5) as glycosyl donors with various glycosyl acceptors provided corresponding disaccharides in high yields. The present CB glycoside methodology was successfully applied to the efficient construction of the tetrasaccharide 41.

carbohydrates - oligosaccharide synthesis - glycosylations - CB glycosides - BCB glycosides

References

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For recent examples of new glycosyl donors and activating systems, see:

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9

The 2′-carboxybenzyl (CB) glycoside seems to be the more appropriate name than the 2-(hydroxycarbonyl)benzyl (HCB) glycoside, which was used in our earlier publication. See, ref. 10

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15

A solution of 40 (32 mg, 0.035 mmol, 1.0 equiv), 38 (39 mg, 0.042 mmol, 1.2 equiv) and 2,6-di-tert-butyl-4-methyl-pyridine (21 mg, 0.11 mmol, 3.0 equiv) in CH₂Cl₂ (5 mL) in the presence of 4A molecular sieves was stirred for 30 min at room temperature and cooled to -40 ºC, then Tf₂O (8.8 µL, 0.055 mmol, 1.5 equiv) was added. The reaction mixture was stirred at -40 ºC for further 1 h and allowed to warm over 2 h to 0 °C. The reaction mixture was quenched with saturated aqueous NaHCO₃ and the organic phase was washed with brine, dried (MgSO₄), concentrated in vacuo. The residue was purified by silica gel flash column chromatography (33% ethyl acetate in hexane) to afford compound 41 (44 mg, 75%): colorless oil, R_f = 0.37 (33% ethyl acetate in hexane); [α]_D ²⁰ = +46.3 (c 1.5, CHCl₃); ¹H NMR (250 MHz, CDCl₃) δ 1.14 (s, 9 H), 3.38-3.47 (m, 2 H), 3.56-3.63 (m, 2 H), 3.69 (dd, J = 3.0 Hz, 5.0 Hz, 1 H), 3.83-3.91 (m, 5 H), 4.00-4.11 (m, 5 H), 4.14 (dd, J = 2.5 Hz, 5.0 Hz, 1 H), 4.22-4.35 (m, 6 H), 4.39-4.47 (m, 2 H), 4.52-4.65 (m, 5 H), 4.70-4.82 (m, 5 H), 4.92 (d, J = 6.0 Hz, 1 H), 5.00-5.12 (m, 3 H), 5.29 (m, 1 H), 5,33 (s, 2 H), 5.53 (s, 1 H), 5.59 (s, 1 H), 5.61 (s, 1 H), 7.06-7.55 (m, 46 H), 7.68 (dd, J = 3.7 Hz, 3.7 Hz, 1 H), 7.94 (d, J = 3.7 Hz, 1 H), 8.00 (d, J = 3.7 Hz, 1 H); ¹³C NMR (63 MHz, CDCl₃) δ 27.3, 39.0, 64.9, 66.7, 67.8, 68.1, 68.4, 68.6, 69.1, 69.6, 70.0, 70.8, 71.4, 72.7, 73.9, 74.4, 74.7, 76.7, 78.6, 80.1, 97.3, 98.0, 98.8, 100.9, 101.4, 101.5, 101.6, 125.8, 125.9, 126.0, 126.1, 127.3, 127.6, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.6, 129.0, 134.0, 137.7, 146.5, 166.7, 177.1, 194.6; Anal. Calcd for C₁₀₀H₁₀₂O₂₄: C, 71.16; H, 6.09. Found: C, 71.15; H, 6.11; MALDI-TOF MS Calcd for 1725.7761 (M + K). Found 1725.7712.