Synthesis of Protected Hexp‐(1 → 4)‐β‐D‐GlcpNAc‐(1 → 2)‐α‐D‐Manp‐(1 → O)(CH2)7CH3 sequences (hex = β‐D‐Glc, 4‐deoxy‐4‐fluoro‐β‐D‐Gal, or 4‐deoxy‐β‐D‐Gal) Using a Glc–GlcNPhth Donor, Eventually Fluorinated or Deoxygenated at the Oligosaccharide Level

Abstract

AbstractThree trisaccharide derivatives of the type β‐D‐Hexp‐(1 → 4)‐β‐D‐GlcpNAc(1 → 2)‐α‐D‐Manp‐(1 → O)(CH2)7CH3 have been synthesized, with Hex being either glucose (15), 4‐deoxy‐4‐fluorogalactose (20), or 4‐deoxygalactose (27). These trisaccharides have been designed for the study of the acceptor specificity of glycosyltransferases involved in termination of N‐acetyllactosamine‐type N‐glycans. Allyl (2‐O‐acetyl‐3,6‐di‐O‐benzyl‐β‐D‐glucopyranosyl)‐(1 → 4)‐3,6‐di‐O‐benzyl‐2‐deoxy‐2‐phthalimido‐β‐D‐glucopyranoside (10) was synthesized by condensation of 2,4,6‐tri‐O‐acetyl‐3‐O‐benzyl‐α‐D‐glucosypanosyl trichloroacetimidate with allyl 3,6‐di‐O‐benzyl‐2‐deoxy‐2‐phthalimido‐β‐D‐glucopyranoside, followed by 4′,6′‐de‐O‐acetylation, 4′,6′‐O‐benzylidenation (8), and specific acetal ring opening. Acetylation or inverted fluorination of 10, followed by deallylation and imidation, gave suitable disaccharide donors which were each condensed with octyl 3,4,6‐tri‐O‐benzyl‐α‐D‐mannopyranoside (14) to afford the fully protected trisaccharides 15 and 20. Deallylation and imidation of 8, followed by coupling to 14 and subsequent specific acetal ring opening, triflation, halogenation, and reductive dehalogenation gave the protected 4″‐deoxytrisaccharide.