Synthesis of S-alkyl esters of protected 2′-deoxyribonucleoside 3′-phosphorothioates. Building blocks for the large-scale synthesis of phosphorothioate analogues of oligodeoxyribonucleotides by the phosphotriester approach in solution

Abstract

Triethylammonium salts of 5′-O-(9-phenylxanthen-9-yl)-2′-deoxyribonucleoside 3′-(H-phosphonates)23, 33a, 33b and 33c, derived from thymidine, 6-N-pivaloyl-2′-deoxyadenosine, 4-N-benzoyl-2′-deoxycytidine and 2-N-phenylacetyl-2′-deoxyguanosine, react with N-(2-cyanoethylsulfanyl)phthalimide 21 in the presence of chlorotrimethylsilane and 4-methylmorpholine to give the corresponding 3′-phosphorothioate S-(2-cyanoethyl) esters 24c, 34a, 34b and 34c, respectively, in good yield. The S-(2-cyanoethyl) group appears to be suitable for the protection of internucleotide linkages in the synthesis of oligonucleotide phosphorothioates by the phosphotriester approach in solution.