OLIGONUCLEOTIDE SYNTHESES ON INSOLUBLE POLYMER SUPPORTS .3. 15 DE(DEOXYRIBONUCLEOSIDE) MONOPHOSPHATES AND SEVERAL TRINUCLEOSIDE DIPHOSPHATES

The previously described insoluble styrene-divinylbenzene copolymer containing methoxylritvl functional groups has been condensed with the N-acylated deoxyribonucleosides N-benzoyldeoxyadenosine, N-anisoyldeoxycytidine, and N-acetyldeoxyguanosine to give the corresponding supported nucleosides in amounts corresponding to 325-360 μmol/g of polymer. Condensation of these products, and a similar thymidine-containing polymer, with the protected nucleotides N-3′-O-diacetyldeoxyadenosine 5′-phosphate, N-anisoyl-3′-O-acet yldeoxycytidine 5′-phosphate, N-3′-O-diacetyldeoxyguanosine 5′-phosphate, and 3′-O-acetylthymidine 5′-phosphate in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride gave 15 dinucleoside phosphates in isolated conversions of 10-60% based on polymer-bound nucleoside. Several dinucleoside monophosphate-containing polymers were 3′-O-deacetylated and further condensed to trinucleoside diphosphate derivatives from which were isolated deoxyadenylyl-(3′→5′)-thymidylyl-(3′→5′)-thymidine (dApTpT), deoxyguanylyl-(3′-→5′)-thymidylyl-(3′→5′)- thymidine (dGTpT), deoxycytidylyl-(3′→5′)-deoxycylidylyl-(3′→5′)-thymidine (dCpCpT), deoxycytidylyl-(3′→5′)-thymidylyl-(3′→5′)-thymidine (dCpTpT), and thymidylyl-(3′→5′)-deoxycytidylyl-(3′→5′)-thymidine (dTpCpT) in conversions of 10-75% based on dinucleoside phosphate. Specific enzymic hydrolysis showed the products to contain exclusively 3′→5′ phospho diester linkages. © 1969, American Chemical Society. All rights reserved.