Bioinspired Total Synthesis and Biological Evaluation of Nucleoside Antibiotics A201E and the Derivatives of A201 Family

Abstract

A modular total synthesis of A201E and its analogues is modeled after the previously reported biosynthetic pathway. The challenging task of obtaining 1,2-cis-furanoside, a vital core structure of A201E and its analogues, was accomplished through the strategic use of remote 2-quinolinecarbonyl-assisted glycosylation. From this pivotal 1,2-cis-furanoside moiety, we successfully completed the total synthesis of A201E and its analogues. Guided by the principles of medicinal chemistry, we evaluated the antimicrobial activities of A201A/E and its analogues. A comprehensive assessment of their antimicrobial activities has illuminated the structure–activity relationship of A201A/E and its analogues. The synthetic strategy we report herein will guide the creation of additional analogues, potentially elucidating the mode of action and addressing a critical area of unmet medical need.