Silane promoted glycosylation and its applications for synthesis of sugar compounds and active pharmaceutical ingredients (APIs)

Abstract

The structural diversity of carbohydrates through glycosylation reactions is the holy grail of carbohydrate chemistry. One or more carbohydrates covalently bonded to another molecule at selective sites by glycosylation/glycoconjugation are often required for better pharmacological activity and their synthesis is apparently more consistent. Selective conjugation of carbohydrates at the –OH group remains a challenge because of the similar reactivity of equivalent polyhydroxyl groups. Eventually a small variety of reagents have been demonstrated to promote site selective glycosylation reactions. Silanes have long provided a leverage in glycosylation reactions since they are easy to install and remove/modify in various synthetic procedures. Regardless of the fact that silanes have proven to be efficient promoters for facile glycoconjugation reactions, a thorough investigation has not been done on this subject. This review discusses the recent application and synthetic usefulness of versatile silanes like trimethylsilyl trifluoromethanesulfonate (TMSOTf), tert-butyldimethylsilyltrifluoromethanesulphonate (TBSOTf), N-(trimethylsilyl)bis(trifluoromethanesulfonyl)imide (TMSNTf₂), potassium bis(trimethylsilyl)amide (KHMDS), trimethylsilyl perchlorate (TMSClO₄), etc. in various site selective glycosylation reactions and also effective methods for the preparation of sugar compounds and active pharmaceutical ingredients (APIs).