Stereoselective entry into the d-GalNAc series starting from the d-Gal one: a new access to N-acetyl-d-galactosamine and derivatives thereof

Abstract

-A new stereoselective preparation of N-aceyl-D-galactosamine (1b) starting from the know pmethoxyphenyl 3,4-O-isopropylidene-6-O-(1-methoxy-1-methylethyl)-β-D-galactopyranoside (10) is described using a simple strategy based on: (a) epimerization at C-2 of 10 via oxidation-reduction to give the talo derivative 11, (b) amination with configurational inversion at C-2 of 11 via a SN2 on its 2-imidazylate, (c) anomeric deprotection of the pmethoxyphenyl β-D-galactosamine glycoside 14, (d) complete deprotection. Applying the same protocol to 2,3:5,6:3',4'-tri-O-isopropylidene-6'-O-(1-methoxy-1-methylethyl)-lactose dimethyl acetal (4), directly obtained through acetonation of lactose, the disaccharide β-D-GalNAcp-(1→4)-D-Glcp (1a) was obtained with complete stereoselectivity in good (40%) overall yield from lactose.

Synthesis and Biological Evaluation of New Glycoconjugated LDH Inhibitors as Anticancer Agents

“…Poliacetonide lactose derivatives have been widely used as suitable protected forms of the natural disaccharide. Indeed, only one or two unprotected hydroxyl groups are left on the galacto non-reducing moiety, which allows for consecutive feasible modifications [22,23,24,25]. Herein, known poliacetonide derivatives 20 [26] was coupled with NHI 1 again through a Mitsunobu condensation with PPh 3 , DMEAD in dry THF giving disaccharide derivative 21 in a good yield (75%, Scheme 2).…”

Stereoselective Access to the β‐D‐N‐Acetylhexosaminyl‐(1→4)‐1‐deoxy‐D‐nojirimycin Disaccharide Series Avoiding the Glycosylation Reaction

“…MgSO 4 was used as the drying agent for solutions. Compound 4‐ O ‐(2‐acetamido‐6‐ O ‐benzyl‐3,4‐ O ‐isopropylidene‐2‐deoxy‐β‐ D ‐talopyranosyl)‐2,3:5,6‐di‐ O ‐isopro‐pylidene‐ aldehydo ‐ D ‐glucose dimethyl acetal ( 6 ),19a 4‐ O ‐(2‐acetamido‐2,6‐di‐ O ‐benzyl‐2‐deoxy‐β‐ D ‐mannopyranosyl)‐2,3:5,6‐di‐ O ‐isopropylidene‐ aldehydo ‐ D ‐glucose dimethyl acetal ( 7 ),19a 4‐ O ‐(2‐azido‐6‐ O ‐benzyl‐3,4‐ O ‐isopropylidene‐2‐deoxy‐β‐ D ‐galactopyranosyl)‐2,3:5,6‐di‐ O ‐isopropylidene‐ aldehydo ‐ D ‐glucose dimethyl acetal ( 8 ),19b 4‐ O ‐(2‐azido‐3,4,6‐tri‐ O ‐benzyl‐2‐deoxy‐β‐ D ‐glucopyranosyl)‐2,3:5,6‐di‐ O ‐isopropylidene‐ aldehydo ‐ D ‐glucose dimethyl acetal ( 9 )19c and 4‐ O ‐(2‐acetamido‐6‐ O ‐benzyl‐2‐deoxy‐β‐ D ‐talopyranosyl)‐2,3‐ O ‐isopropylidene‐ aldehydo ‐ D ‐glucose dimethyl acetal ( 10 )19a were prepared according to the reported procedures.…”

A Sulfamate-Tethered Aza-Wacker Cyclization Strategy for the Syntheses of 2-Amino-2-Deoxyhexoses: Preparation of Orthogonally Protected D-Galactosamines

“…1,4 D-galactosamine and N-acetyl-D-galactosamine are obtainable from hydrolysis of chondroitin sulfates, 5 but differentially protected derivatives require total syntheses. To date, almost all orthogonally protected D-galactosamines have been prepared using "heterocycle➔heterocycle" approaches (Scheme 1A) with either glycals [6][7][8] or other hexoses [9][10][11][12][13][14] as starting materials. 15 Diverse alkene functionalization reactions have been employed for the transformation of glycals into D-galactosamine derivatives.…”