THE AUTOMATED SYNTHESIS OF SULFUR-CONTAINING OLIGODEOXYRIBONUCLEOTIDES USING 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE AS A SULFUR-TRANSFER REAGENT

Several polysulfides were tested as potential sulfur-transfer reagents during the automated synthesis of oligodeoxyribonucleoside phosphorothioates via the “deoxyribonucleoside phosphoramidite” approach. The thiosulfonate 3H-l,2-benzodithiol-3-one 1,1-dioxide (12) was particularly efficient as a sulfurizing reagent. A 0.2 M solution of 12 in acetonitrile converted the dinucleoside monophosphite triesters 13a-d into the corresponding phosphorothioates 15a-d within 30 s in near quantitative yields. This reagent led to rapid, efficient (stepwise yields of 99%), and reliable automated synthesis of phosphorothioate oligomers (28-mers) complementary to the mRNA of the HIV-1 rev gene, carrying either exclusively or a predetermined number of P(S) linkages. Additionally, oligomers exposed to prolonged treatment (24 h) with the sulfurizing reagent did not show any detectable modification of the nucleosidic bases. © 1990, American Chemical Society. All rights reserved.