Synthesis of Novel Pseudodisaccharides and Neoglycoconjugates Containing an N-Glycosyl Carbamate Backbone

Abstract

A new class of pseudodisaccharides is presented in which a N-glycosyl carbamate is connected to a monosaccharide unit, using a mild and stereo-controlled isocyanide approach. The methodology was extended to the case of neoglycoconjugates ­useful as synthons for the construction of molecules with potential therapeutic interest.

carbohydrates - glycosyl carbamates - oligosaccharides - isocyanate - glycoconjugates

References

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9

Selected data for compound 1a. Mp 63-65 °C; [α]_D ²³ +14.1 (c 1.00, CHCl₃). ¹H NMR (200 MHz, CDCl₃): δ = 1.94 (3 H, s, OAc), 2.01 (3 H, s, OAc), 2.02 (3 H, s, OAc), 2.07 (3 H, s, OAc), 3.35 (3 H, s, OMe), 3.41 (1 H, dd, J = 9.6, 1.5 Hz, H-6a), 3.51 (1 H, dd, J = 9.6, 3.4 Hz, H-6b), 3.72-3.86 (2 H, m, H-5, H-5′), 3.99 (1 H, t, J = 9.2 Hz, H-3), 4.07 (1 H, dd, J = 12.6, 1.1 Hz, H-6a′), 4.19-4.37 (2 H, m, H-4, H-6b′), 4.48-5.13 (9 H, m, H-1, H-2′, H-4′, 3 CH₂Ph), 5.01 (1 H, d, J = 8.9 Hz, H-1′), 5.29 (1 H, t, J = 9.3 Hz, H-3′), 5.63 (1 H, br d, J = 9.5 Hz, NH), 7.20-7.41 (15 H, m, Ph). ¹³C NMR (50 MHz, CDCl₃): δ = 20.5, 55.2, 61.5, 64.4, 68.0, 68.6, 70.2, 72.7, 73.2, 73.4, 75.0, 75.7, 77.6, 79.8, 80.7, 81.8, 97.9, 127.6, 127.9, 128.1, 128.4, 137.8, 137.9, 138.5, 155.2, 169.5, 169.9, 170.5.

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12a

Procedure for the Deprotection of 1a: Compound 1a (90 mg, 0.11 mmol) was hydrogenated in MeOH (2 mL) in the presence of a catalytic amount of Pd/C; the crude product was deacetylated in methanolic NaOMe (0.02 mmol), giving 44 mg of 4a, with a 100% overall yield.

12b

Deprotection of 1d: To a solution of compound 1d (109 mg, 0.13 mmol) in CH₂Cl₂ (2 mL), 90% aq TFA (620 µL) was added; after 1.5 h, the mixture was diluted with CH₂Cl₂ (15 mL) and washed with a sat. solution of NaHCO₃ (10 mL). The organic layer was dried over Na₂SO₄ and the solvent was evaporated. The crude product was dissolved in dry MeOH (4 mL) and 70 µL of a 1 M solution of NaOMe (0.07 mmol) were added, furnishing 60 mg of 4d (92%) as a white solid after flash chromatography.

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20

Selected data for Compound 11: [α]_D ²¹ +40.1 (c 1.00, MeOH). ¹H NMR (300 MHz, CD₃OD): δ = 1.11-3.16 (10 H, m, BH), 3.45 (1 H, ddd, J = 9.0, 4.8, 3.1 Hz, H-5), 3.66 (1 H, t, J = 9.0 Hz, H-4), 3.70-3.77 (3 H, m, H-3, H-6a, H-6b), 3.80, (1 H, dd, J = 2.8, 1.8 Hz, H-2), 4.58 (1 H, br s, carboranyl CH), 4.63 (2 H, s, CH₂), 5.26 (1 H, d, J = 1.8 Hz, H-1). ¹³C NMR (75 MHz, CD₃OD): δ = 63.0, 66.4, 69.0, 72.0, 72.5, 76.1, 82.6, 156.8.