SYNTHESIS OF OLIGOTHYMIDYLATES VIA PHOSPHOTRIESTER INTERMEDIATES

A procedure is described for the large-scale preparation of β-cyanoethyl ester derivatives of 5ʹ-O-monomethoxytrityl TpT, TpTpT, and TpTpTpT. The essential feature is a double phosphorylation, the first step of which involves reaction of a terminal 3ʹ-OH of a nucleoside with β-cyanoethyl phosphate and mesitylene sulfonyl chloride and the second step, condensation of the resulting phosphodiester with thymidine in the presence of triisopropylbenzenesulfonyl chloride. The products are separated by chromatography on silica gel with ethyl acetate and tetrahydrofuran. They may be converted in high yield to the corresponding demethoxytritylated derivatives and thence to TpT, TpTpT, and TpTpTpT, respectively, by successive treatment with aqueous acetic acid and ammonium hydroxide. © 1969, American Chemical Society. All rights reserved.