Synthesis of Norcarbovir Analogues, the First Examples of Cyclobutene Nucleosides Unsubstituted at the Vinylic Position.
Two cyclobutene nucleosides, 27 and 29, analogous to the yet unknown norcarbovir, and with adenine and hypoxanthine as the base moieties, respectively, were synthesized starting from cis-3-cyclobutene-1,2-dicarboxylic anhydride (6). Its reduction to lactone 9 followed by reaction with ammonia and then Hofmann rearrangement led to cyclic carbamate 15 which was the key intermediate of these syntheses. Its tert-butoxycarbonyl derivative 17 led to the ring opening of the heterocyclic moiety at low temperature. Compound 18 was thus obtained, and the successive benzylation and then treatment with hydrochloric acid yielded hydrochloride 21. Construction of bases was achieved in satisfying overall yields provided that mild experimental conditions from 21 to 27 or 29 were used to restrict the unwanted electrocyclic ring opening. Nitropyrimidine 31 was also prepared from 21 via the intermediate 23.
Gourdel-Martin
Marie-Edith
ME
Laboratoire de Synthèse Organique, URA-CNRS 482, Faculté des Sciences, Université du Maine, BP 535, F-72017 Le Mans Cedex, France.
Huet
François
F