Synthesis of Modified Nucleoside Oligophosphates Simplified: Fast, Pure, and Protecting Group Free

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2019 Sep 13

PMID 31512870

Citations 14

Authors

Jyoti Singh

Alexander Ripp

Thomas M Haas

Danye Qiu

Manfred Keller

Paul A Wender

Jay S Siegel

Kim K Baldridge

Henning J Jessen

Affiliations

Soon will be listed here.

Abstract

Phosphoramidite analogues of modified cyclotriphosphates provide a general and step-economical synthesis of nucleoside triphosphates and analogues on scale without the need for protecting groups. These reagents enable rapid access to pure nucleoside oligophosphates and a range of other analogues that were previously difficult to obtain (e.g., NH, CH, CCl, and CF replacements for O, phosphono- and phosphoimidazolides, -morpholidates, -azidates, and -fluoridates). DFT calculations demonstrate that the selectivity of the cyclotriphosphate opening reactions proceeds via an in-line substitution mechanism that displaces the least charged leaving group.

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