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Site-Selective Switching Strategies to Functionalize Polyazines.

ABSTRACT: Many drug fragments and therapeutic compounds contain multiple pyridines and diazines. Developing site-selective reactions where specific C-H bonds can be transformed in polyazine structures would enable rapid access to valuable derivatives. We present a study that addresses this challenge by selectively installing a phosphonium ion as a versatile functional handle. Inherent factors that control site-selectivity are described along with mechanistically driven approaches for site-selective switching, where the C-+PPh3 group can be predictably installed at other positions in the polyazine system. Simple protocols, readily available reagents, and application to complex drug-like molecules make this approach appealing to medicinal chemists.

SUBMITTER: Dolewski RD

PROVIDER: S-EPMC6280969 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Site-Selective Switching Strategies to Functionalize Polyazines.

Dolewski Ryan D RD Fricke Patrick J PJ McNally Andrew A

Journal of the American Chemical Society 20180524 25

Many drug fragments and therapeutic compounds contain multiple pyridines and diazines. Developing site-selective reactions where specific C-H bonds can be transformed in polyazine structures would enable rapid access to valuable derivatives. We present a study that addresses this challenge by selectively installing a phosphonium ion as a versatile functional handle. Inherent factors that control site-selectivity are described along with mechanistically driven approaches for site-selective switch ...[more]

PMID: 29792698

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