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

• DOI: 10.1021/acs.joc.1c01055
• Publication Date: 2021-07-07T19:54:10Z
• Authors: Bin Zheng; Chao Hang; Jason Zhu; Geoffrey E. Purdum; Melda Sezen-Edmonds; Daniel S. Treitler; Miao Yu; Changxia Yuan; Ye Zhu; Adam Freitag; Siwei Guo; Guanghui Zhu; Ben Hritzko; James Paulson; Jonathan G. Shackman; Brian L. He; Weiqing Fu; Hua Chia Tai; Sloan Ayers; Hyunsoo Park; Martin D. Eastgate; Ben Cohen; Amanda Rogers; Qinggang Wang; Michael A. Schmidt
• Keywords: Membrane Proteins; Indicators and Reagents; 01 natural sciences; 0104 chemical sciences

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 specially designed P(V) reagent. By utilizing this strategy, CDN was prepared in greater than 16-fold higher yield prior P(III) approach, fewer hazardous reagents chromatographic purifications.