SYNTHESIS OF METHYLENE-EXPANDED 2',3'-DIDEOXYRIBONUCLEOSIDES

A method for the preparation of methylene-expanded 2',3'-dideoxyribonu cleosides is reported. The very inexpensive starting material levogluc osenone 8 was converted into the known mixture of alcohols 12ab which were converted into the required silyl ether alcohol 26 in six steps v ia either of two routes. The first involved a one-step acetylation and opening of the anhydro sugar bridge to give the triacetates 20ab whic h were reduced with triethylsilane and silyl triflate to afford the di acetates 21ab, both of which gave 26 after further functional group co nversions. The second route entailed a simple acetylation of 12ab foll owed by reduction with triethylsilane and silyl triflate to give the m onoacetates 19ab, both converted via straightforward chemistry into 26 . Mesylation of the alcohol of 26 furnished the mesylate 27. Alkylatio n of adenine with the mesylate 27 afforded the silyl ether 28 which wa s deprotected to give the desired modified dideoxy nucleoside 7a. Alky lation of 2,6-diaminopurine 38 with the mesylate gave the protected di aminopurine nucleoside 39. Upon acetylation, it produced a mixture of di- and monoacetates 40-41, the latter of which was transformed into t he desired guanosine analogue 7e. Thus, two new nucleoside analogues 7 ae were prepared from levoglucosenone 8.