P(III) vs P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to an Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophos­phoramidate linkages is described. These rare yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P­(V) reagent. By utilizing this strategy, the CDN was prepared in greater than 16-fold higher yield than the prior P­(III) approach, with fewer hazardous reagents and chromatographic purifications.