A NEW EFFICIENT SYNTHESIS OF ANTIVIRAL METHYLENECYCLOPROPANE ANALOGS OF PURINE NUCLEOSIDES

New synthetic approach to antiviral agents synadenol (la) and 2-amino- 6-chloropurine analog Ic is described. Alkylating agents 10a + 10b, 11 and 12a + 12b were obtained by reduction of ethyl 2-bromo-2-(bromomet hyl)cyclopropane-1-carboxylates (4) followed by protection of the hydr oxy function. Partial halogen exchange at the 2-bromomethyl group was observed with reagents containing chlorine. These agents were employed in alkylation-elimination sequence with adenine (3a) and 2-amino-6-ch loropurine (3c) to give intermediates 13a-13e and 14a-14e. The Z- and E-isomers of MOM derivatives 13b and 14b were separated by chromatogra phy and the former was deprotected to give synadenol (la). Deprotectio n of 13a + 14a, 13c + 14c and 13d + 14d afforded la + 2a and Ic + 2c. From the latter mixture Ic was obtained by chromatography.