Reactions of 2-acyloxyisobutyryl halides with nucleosides. 8. Synthesis and biological evaluation of some 3'-acyl and 3',5'-diacyl derivatives of 1-.beta.-D-arabinofuranosylcytosine

Abstract

Previous papers in this series described efficient syntheses of 3''-O-acyl and 3'',5''-di-O-acyl derivatives of 2,2''-anhydro-1-(.beta.-D-arabinofuranosyl)cytosine [araC] hydrochloride (1,3). The 2,2''-anhydro linkage in 1 and 3 can be selectively and efficiently cleaved by treatment with a mixture of pyridine and methanol giving the corresponding 3''-O-acyl and 3'',5''-di-O-acyl derivatives of araC (2,4). The selective hydrolysis of the more soluble derivatives can also be achieved using aqueous pyridine or a mixture of sodium carbonate and sodium bicarbonate in aqueous dioxane. Using the above procedures 3''-O-acyl araC''s and 3'',5''-di-O-acyl araC''s with saturated or unsaturated ester groups containing 2-22 C atoms were prepared, and these substances were evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity against L1210 leukemia in mice. Many of the compounds show high anti-L1210 activity relative to araC itself.