A large-scale synthesis of 3,4,5-tri-0-acetyl-2,6-anhydro-L-mannono-and-D-gulonothioamides
(5, 6) has been achieved from the corresponding nitriles. The Hantzsch 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 some 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).
New tiazofurin analogues (1-5) have been synthesized starting from the corresponding
thioamides.
