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

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, CH₂, CCl₂, and CF₂ 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.

SUBMITTER: Singh J

PROVIDER: S-EPMC10044464 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Singh Jyoti J Ripp Alexander A Haas Thomas M TM Qiu Danye D Keller Manfred M Wender Paul A PA Siegel Jay S JS Baldridge Kim K KK Jessen Henning J HJ

Journal of the American Chemical Society 20190913 38

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, CH2, CCl2, and CF2 replacements for O, phosphono- and phosphoimidazolides, -morpholidates, -azidates, and -fluoridates ...[more]

PMID: 31512870

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