Novel method for the synthesis of dinucleoside-(N3 ' -> P5 ')-phosphoramidothioates

摘要

A new approach for the synthesis of dinucleoside-(N3'-> P5')-phosphoramidothioates based on the Atherton Todd reaction has been developed using nucleoside H-thiophosphonates and 3'-amino-2',3'-dideoxynucleosides with an unprotected 5'-hydroxyl group. A mixture of P-diastereomers of dinucleosides was separated by column chromatography into fast migrating and slow migrating isomers. Based on single crystal X-ray diffraction analysis, the absolute configuration at the phosphorus atom in the slow eluting diastereomer of the dinucleoside-(N3' -> P5')-phosphoramidothioate G(Nps)G(NHTr) was assigned as Rp. (C) 2017 Elsevier Ltd. All rights reserved.