Structural Revision of Baulamycin A and Structure-Activity Relationships of Baulamycin A Derivatives

Sandip Sengupta, Munhyung Bae, Dong Chan Oh, Uttam Dash, Hak Joong Kim, Woon Young Song, Injae Shin, Taebo Sim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Total synthesis of the proposed structure of baulamycin A was performed. The spectral properties of the synthetic compound differ from those reported for the natural product. On the basis of comprehensive NMR study, we proposed two other possible structures for natural baulamycin A. Total syntheses of these two substances were performed, which enabled assignment of the correct structure of baulamycin A. Key features of the convergent and fully stereocontrolled route include Evans Aldol and Brown allylation reactions to construct the left fragment, a prolinol amide-derived alkylation/desymmetrization to install the methyl-substituted centers in the right fragment, and finally, a Carreira alkynylation to join both fragments. In addition, we have determined the inhibitory activities of novel baulamycin A derivatives against the enzyme SbnE. This SAR study provides useful insight into the design of novel SbnE inhibitors that overcome the drug resistance of pathogens, which cause life-threatening infections.

Original languageEnglish
Pages (from-to)12947-12966
Number of pages20
JournalJournal of Organic Chemistry
Volume82
Issue number24
DOIs
Publication statusPublished - 2017 Dec 15

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Alkylation
Structure-Activity Relationship
Biological Products
Drug Resistance
Amides
Allylation
Derivatives
Pathogens
Enzymes
Infection
Nuclear magnetic resonance
Pharmaceutical Preparations
prolinol
3-hydroxybutanal

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Structural Revision of Baulamycin A and Structure-Activity Relationships of Baulamycin A Derivatives. / Sengupta, Sandip; Bae, Munhyung; Oh, Dong Chan; Dash, Uttam; Kim, Hak Joong; Song, Woon Young; Shin, Injae; Sim, Taebo.

In: Journal of Organic Chemistry, Vol. 82, No. 24, 15.12.2017, p. 12947-12966.

Research output: Contribution to journalArticle

Sengupta, Sandip ; Bae, Munhyung ; Oh, Dong Chan ; Dash, Uttam ; Kim, Hak Joong ; Song, Woon Young ; Shin, Injae ; Sim, Taebo. / Structural Revision of Baulamycin A and Structure-Activity Relationships of Baulamycin A Derivatives. In: Journal of Organic Chemistry. 2017 ; Vol. 82, No. 24. pp. 12947-12966.
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