Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate

Discovery of potential mPTP blockers

Sun Hwa Jung, Kihang Choi, Ae Nim Pae, Jae Kyun Lee, Hyunah Choo, Gyochang Keum, Yong Seo Cho, Sun Joon Min

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

This article describes the rapid and diversified synthesis of pyrrolidinyl triazoles for the discovery of mitochondrial permeability transition pore (mPTP) blockers. The 1,3-dipolar cycloaddition of ethynyl trifluoroborate with azidopyrrolidine produced a key intermediate, triazolyl trifluoroborate 4, which subsequently underwent a Suzuki-Miyaura coupling reaction to afford a series of 1,4-disubstituted triazoles 2. Subsequent biological evaluation of these derivatives indicated 2ag and 2aj as the most potent mPTP blockers exhibiting excellent cytochrome P450 (CYP) stability when compared to the previously reported oxime analogue 1. The present work clearly demonstrates that a 1,2,3-triazole can be used as a stable oxime surrogate. Furthermore, it suggests that late-stage diversification through coupling reactions of organotrifluoroborates is suitable for the rapid discovery of biologically active molecules. This journal is

Original languageEnglish
Pages (from-to)9674-9682
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number47
DOIs
Publication statusPublished - 2014 Dec 21

Fingerprint

Triazoles
permeability
Oximes
porosity
cytochromes
cycloaddition
synthesis
Cycloaddition
Cycloaddition Reaction
analogs
Cytochrome P-450 Enzyme System
evaluation
Derivatives
molecules
Molecules
mitochondrial permeability transition pore

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate : Discovery of potential mPTP blockers. / Jung, Sun Hwa; Choi, Kihang; Pae, Ae Nim; Lee, Jae Kyun; Choo, Hyunah; Keum, Gyochang; Cho, Yong Seo; Min, Sun Joon.

In: Organic and Biomolecular Chemistry, Vol. 12, No. 47, 21.12.2014, p. 9674-9682.

Research output: Contribution to journalArticle

Jung, Sun Hwa ; Choi, Kihang ; Pae, Ae Nim ; Lee, Jae Kyun ; Choo, Hyunah ; Keum, Gyochang ; Cho, Yong Seo ; Min, Sun Joon. / Facile diverted synthesis of pyrrolidinyl triazoles using organotrifluoroborate : Discovery of potential mPTP blockers. In: Organic and Biomolecular Chemistry. 2014 ; Vol. 12, No. 47. pp. 9674-9682.
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