Oligonucleosides with a nucleobase-including backbone - Part 2 - Synthesisand structure determination of adenosine-derived monomers

The synthesis and structure determination of adenosine-derived monomeric bu ilding blocks for new oligonucleosides are described. Addition of Me,Si-ace tylide to the aldehyde derived from the known partially protected adenosine 1 led to the epimeric propargylic alcohols 2 and 3, which were oxidised to the same ketone 4, while silylation and deprotection led to 7 and 9 (Schem e I). Introduction of an I substituent at C(8) of the propargylic silyl eth ers 10 and 11 was not satisfactory. The protected adenosine 12 was, therefo re, transformed in high yield into the 8-chloro derivative 13 by deprotonat ion and treatment with PhSO2Cl; the iodide 15 was obtained in a similar way (Scheme 2). The 8-Cl and the 8-I derivatives 13 and 15 were transformed in to the propargylic alcohols 17 18, 25, and 26, respectively (Scheme 3). The propargylic derivatives 2, 10, 17 19, 23, 25, and 27 were correlated, and their (5'R) configuration was determined on the basis of NOEs of the anhydr o nucleoside 19; similarly, correlation of 3, 11, 18, 20, 24, 26, and 28, a nd NOE's of 20 evidenced their (5'S)configuration.