NUCLEOSIDE S-ALKYL PHOSPHOROTHIOATES .3. APPLICATION TO OLIGONUCLEOTIDE SYNTHESIS

The S-ethyl phosphorothioate group has been used as a protecting group in oligonucleotide synthesis. Nucleoside 5 ′-S-ethyl phosphorothioates were condensed with several partially protected mononucleotides to give a series of dinucleotides containing 5′-S-ethyl phosphorothioate groups. These were partially unblocked and converted into the corresponding trinucleotide 5 ′-S-ethyl phosphorothioates by further condensation. The acyl groups of the fully protected di- and trinucleotide S-ethyl phosphorothioates could be removed with aqueous ammonia without destruction of the S-ethyl moiety. S-Ethyl di- and trinucleotides were used as intermediates in the preparation of a variety of derivatives; (a) treatment with aqueous iodine removed the S-ethyl group and gave the corresponding unprotected oligomers, (b) treatment with iodine in methanol produced the corresponding 5 ′-methyl esters, (c) treatment with iodine and inorganic pyrophosphate gave the corresponding oligomer 5 ′-triphosphates, and (d) treatment of an S-ethyl trinucleotide with acetylated adenosine 5 -phosphate gave, after subsequent de-acetylation, a 5′,5′-pyrophosphate derivative of the trimer with adenosine 5′-phosphate. Thymidine 5′-S-ethyl phosphorothioate (1) has been self-condensed using iodine in pyridine, and a series of linear and cyclic oligonucleotides was isolated. © 1969, American Chemical Society. All rights reserved.