Synthesis of novel pyrophosphorothiolate-linked dinucleoside cap analogues in a ball mill

Abstract

Michaelis-Arbuzov reactions of S-aryl disulfide derivatives of 3'-thiothymidine or 5'-thioadenosine with tris(trimethylsilyl) phosphite proceeded in high yields to the corresponding phosphorothiolate monoesters. Subsequent hydrolytic desilylation and phosphate coupling were effected in one-pot using liquid-assisted grinding in a vibration ball mill. Novel 3',5'- and 5',5'-pyrophosphorothiolate-linked dinucleoside cap analogues were thereby prepared.