Significant substituent effect on the anomerization of pyranosides: Mechanism of anomerization and synthesis of a 1,2-cis glucosamine oligomer from the 1,2-trans anomer

Abstract

Aminoglycosides containing a 2,3-trans carbamate group easily undergo anomerization from the 1,2-trans glycoside to the 1,2-cis isomer under mild acidic conditions. The N-substituent of the carbamate has a significant effect on the anomerization reaction; in particular, an N-acetyl group facilitated rapid and complete α-anomerization. The differences in reactivity due to the various N-substituents were supported by the results of DFT calculations; the orientation of the acetyl carbonyl group close to the anomeric position was found to contribute significantly to the directing of the anomerization reaction. By exploiting this reaction, oligoaminoglycosides with multiple 1,2-cis glycosidic bonds were generated from 1,2-trans glycosides in a one-step process. Many bonds make light work! The N-acetyl group on the carbamate affects the trans/cis anomerization of aminoglycosides with 2,3-trans carbamate groups, under mild acidic conditions through endocyclic cleavage (see scheme). DFT calculations revealed that the acetyl carbonyl is close to the anomeric position. Oligoaminoglycosides with multiple 1,2-cis glycosidic bonds were generated in one step from 1,2-trans glycosides. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.