Comparison of Several Glucuronate Glycosyl Donors

Abstract

Methyl 3,4‐di‐O‐benzyl‐[(S)‐1,2‐O‐(1‐cyanoethylidene)]‐α‐d‐glucopyranuronate (12), methyl 3,4‐di‐O‐benzyl‐[(S)‐1,2‐O‐(1‐ethoxyethylidene)]‐α‐d‐glucopyranuronate (14), methyl 2‐O‐acetyl‐3,4‐di‐O‐benzyl‐α‐d‐glucopyranuronate bromide (15), methyl (2‐O‐acetyl‐3,4‐di‐O‐benzyl‐α‐d‐glucopyranosyl)uronate trichloroacetimidate (17), and methyl (2,3,4‐tri‐O‐benzyl‐α/β‐d‐glucopyranosyl)uronate trichloroacetimidate (30) were synthesized and used as glycosyl donors. Glycosylation reactions of 12 with (5‐R)‐2,3,4,5 − tetrahydro‐5‐trityloxymethyl‐2‐furanone (32) and 14,15,17 with the corresponding (5‐R)‐2,3,4,5‐tetrahydro‐5‐hydroxymethyl‐2‐furanone (31) provided the exclusively β‐linked glucuronide 33 in 69%, 28%, 45%, and 71% yield, respectively. The coupling of donor 30 with acceptor 31 furnished the glucuronated lactone 35 in 70% yield with a surprisingly high content (20%) of the undesired α‐linked sugar residue. The structure of 33 was proved by NMR and X‐ray diffraction studies. In a model reaction a complete deprotection procedure of the glucuronic acid lactone conjugation was demonstrated.

Keywords:

• d‐glucuronic acid derivatives
• Orthoesters
• Trichloroacetimidates
• Cyanoethylidene derivatives
• Glycosylation
• X‐ray structures

Acknowledgments

The authors are grateful to the Deutschen Forschungsgemeinschaft as well as the Fonds der Chemischen Industrie for financial support.