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

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. (C) 1999 Elsevier Science Ltd. All rights reserved.