Improved synthesis of capuramycin and its analogues

Yong Wang, Shajila Siricilla, Bilal A. Aleiwi, Michio Kurosu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Capuramycin and its congeners are considered to be important lead molecules for the development of a new drug for multidrug-resistant (MDR) Mycobacterium tuberculosis infections. Extensive structure-activity relationship studies of capuramycin to improve the efficacy have been limited because of difficulties in selectively chemically modifying the desired position(s) of the natural product with biologically interesting functional groups. We have developed efficient syntheses of capuramycin and its analogues by using new protecting groups, derived from the chiral (chloro-4-methoxyphenyl)(chlorophenyl)methanols, for the uridine ureido nitrogen and primary alcohol. The chiral nonracemic (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)methanol derivative is a useful reagent to resolve rac-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin- 2-one, the (S)-configuration isomer of which plays a significant role in improving the mycobactericidal activity of capuramycin. Battling TB: Capuramycin and its congeners (see scheme) are considered to be important lead molecules for the development of a new drug for multidrug-resistant Mycobacterium tuberculosis infections. Efficient synthesis of capuramycin and its analogues by using new protecting groups for the uridine ureido nitrogen and primary alcohol was accomplished.

Original languageEnglish (US)
Pages (from-to)13847-13858
Number of pages12
JournalChemistry - A European Journal
Volume19
Issue number41
DOIs
StatePublished - Oct 4 2013

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Methanol
Alcohols
Nitrogen
Molecules
Isomers
Functional groups
Uridine
Derivatives
Biological Products
Pharmaceutical Preparations
capuramycin

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Improved synthesis of capuramycin and its analogues. / Wang, Yong; Siricilla, Shajila; Aleiwi, Bilal A.; Kurosu, Michio.

In: Chemistry - A European Journal, Vol. 19, No. 41, 04.10.2013, p. 13847-13858.

Research output: Contribution to journalArticle

Wang, Yong ; Siricilla, Shajila ; Aleiwi, Bilal A. ; Kurosu, Michio. / Improved synthesis of capuramycin and its analogues. In: Chemistry - A European Journal. 2013 ; Vol. 19, No. 41. pp. 13847-13858.
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