Carbonyl to methylene conversions at the tricarbonyl-portion of ascomycin derivatives

Abstract

Treatment of ascomycin or its O-TBDMS-derivatives with hydrogen sulfide and pyridine in dimethylformamide solution results in deoxygenation reactions at the tricarbonyl sequence of the binding domain. 9-deoxo-ascomycins ( 5a-c) are obtained in high yields (75–85%) together with small amounts (2–14% yield) of 10-deoxo-ascomycins ( 6a-c). The novel derivative 10-deoxo-ascomycin ( 6a) is accessible in excellent yield (85%) from the 10-amino-analog of ascomycin upon reaction with hydrogen sulfide in the absence of base.