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

preprint
submitted on 12.03.2021, 13:41 and posted on 16.03.2021, 06:48 by Bin Zheng, Chao Hang, Jason Zhu, Geoffrey Purdum, Melda Sezen-Edmonds, Daniel Treitler, Miao Yu, Changxia Yuan, Ye Zhu, Adam Freitag, Siwei Guo, Guanghui Zhu, Benjamin Hritzko, James Paulson, Jonanthan Shackman, Brian He, Weiqing Fu, HuaChia Tai, Sloan Ayers, Hyunsoo Park, Martin Eastgate, Benjamin Cohen, Amanda Rogers, Qinggang Wang, Michael A. Schmidt
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 sixteen-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications.

History

Email Address of Submitting Author

Michael.Schmidt@bms.com

Institution

Bristol Myers Squibb

Country

United States of America

ORCID For Submitting Author

0000-0002-4880-2083

Declaration of Conflict of Interest

No Conflicts of Interest

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