Thiazole C-nucleosides. III. Synthesis of pyranose analogues of tiazofurin

Article abstract of DOI:10.1016/S0040-4020(01)80985-6

A large-scale synthesis of 3,4,5-tro-O-acetyl-2,6-anhydro-L-mannono- and D-gulonothioamides (5, 6) has been achieved from the corresponding nitriles. The Hantsch reaction of (5) or (6) with ethyl bromopyruvate afforded the expected thiazoles (7, 8) only in a low yield along with furan derivatives (9-11), the formation of which is rationalized by an acid-catalysed rearrangement-elimination process. The same Hantzsch reaction in the presence of barium carbonate yielded hydroxythiazolines (16, 17). Attempted dehydration of (16) or (17) with trifluoroacetic anhydride or trifluoroacetic anhydride/pyridine resulted in the formation of pent-1'-enopyranosylthiazoles (18-20). Deprotected thioamides (24, 25) furnished with ethyl bromopyruvate thiazoles (27, 28). The obtained thiazole esters (7, 8, 18-20, 27, 28) were transformed into new tiazofurin analogues (12, 13, 21-23).