Synthesis of oligodeoxynucleotides using the oxidatively cleavable 4-methoxytritylthio (MMTrS) group for protection of the 5′-hydroxylgroup

Abstract

We examined the synthesis of oligodeoxynucleotides containing all four nucleobases using the 4-methoxytritylthio (MMTrS) group for protection of the 5′-hydroxyl group. The MMTrS group could be introduced into 3′-O-TBDMS-deoxycytidine, -deoxyadenosine and -deoxyguanosine with the appropriate base protecting groups using strong bases such as n-butyl lithium and lithium hexamethyldisilazide. Because the MMTrS group could be removed by oxidation with an aqueous I₂ solution, the oxidation of internucleotidic phosphite intermediates could be performed simultaneously. Thus, the nucleotide chain could be extended in a three-step protocol that comprised coupling, capping and oxidation/deprotection. Oligodeoxynucleotides with 10 and 20 mixed-base sequences could be synthesized using this protocol.