Stereoselective Synthesis of a Tetrasaccharide Fragment from Cellulosome Produced by Clostridium thermocellum

Abstract

An efficient synthesis of a structurally congested tetrasaccharide portion from the cellulosome produced by Clostridium thermocellum has been accomplished through a stepwise glycosylation strategy. The key steps for the synthesis include the stereocontrolled construction of a range of challenging 1,2‐cis glycosidic linkages. The 5‐O‐(2‐quinolinecarbonyl) substituted D‐galactofuranosyl thioglycoside 2, 4,6‐O‐benzylidene protected 2‐azido‐2‐deoxyglucose thioglycoside 3 c, and 4,6‐O‐benzylidene protected D‐galactopyranosyl thioglycoside 4 were employed as glycosyl donors, respectively, for the high‐yielding and stereoselective formation of the corresponding 1,2‐cis‐α‐Galf, α‐GlcNAc, and α‐Galp linkages.

Influence of Remote Picolinyl and Picoloyl Stereodirecting Groups for the Stereoselective Glycosylation

“…The same steps was repeated and after two glycosylations, levantetrose 166 was produced in 75% yield with high β-Stereoselectivity (Scheme 39). [55] Recently, Jin-Song Yang and group [56] came up with an innovative idea of using 5-O-(2-quinolinecarbonyl) substituted D-galactofuranosyl thioglycoside 167 that also orthogonally protected at the C2 and C3 positions by a tertbutyldimethylsilyl (TBS) and a levulinoyl (Lev) groups, respectively, which will make it possible to regioselectively incorporate other sugars at these positions, 4,6-O-benzylidene protected 2-azido-2-deoxyglucose thioglycoside 171, and 4,6-O-benzylidene protected Dgalactopyranosyl thioglycoside 170 as glycosyl donors respectively for synthesizing tetrasaccharide which is a backbone of cellulosome produced by Clostridium thermocellum that undergo stepwise glycosylation with acceptor 168 under N-iodosuccinimide (NIS) and catalytic triflic acid (TfOH) condition via 1,2-cisα-Galf, α-GlcNAc, and α-Galp linkages respectively to furnished fully protected tetrasaccharide, which upon global deprotection produced the desired tetrasaccharide 172 in 54% yield (Scheme 40). This glycosylation method takes advantage of the intermolecular hydrogen bonding formed between the Quin group on donor and the hydroxyl group on acceptor to direct the nucleophilic attack of acceptor on the oxocarbenium ion intermediate from the α-face, hence resulting in α-linked galactofuranosides.…”