Stereocontrolled Total Synthesis of Muraymycin D1 Having a Dual Mode of Action against Mycobacterium tuberculosis

Katsuhiko Mitachi, Bilal A. Aleiwi, Christopher M. Schneider, Shajila Siricilla, Michio Kurosu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A stereocontrolled first total synthesis of muraymycin D1 (1) has been achieved. The synthetic route is highly stereoselective, featuring (1) selective β-ribosylation of the C2-methylated amino ribose, (2) selective Strecker reaction, and (3) ring-opening reaction of a diastereomeric mixture of a diaminolactone to synthesize muraymycidine (epi-capreomycidine). The acid-cleavable protecting groups for secondary alcohol and uridine ureido nitrogen are applied for simultaneous deprotections with the Boc and tBu groups. Muraymycin D1 (1) and its amide derivatives (2 and 3) exhibited growth inhibitory activity against Mycobacterium tuberculosis (MIC50 = 1.56-6.25 μg/mL) and strong enzyme inhibitory activities against the bacterial phosphotransferases (MurX and WecA) (IC50 = 0.096-0.69 μM).

Original languageEnglish (US)
Pages (from-to)12975-12980
Number of pages6
JournalJournal of the American Chemical Society
Volume138
Issue number39
DOIs
StatePublished - Oct 5 2016

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Ribose
Uridine
Enzyme activity
Amides
Mycobacterium tuberculosis
Inhibitory Concentration 50
Alcohols
Phosphotransferases
Nitrogen
Derivatives
Acids
Enzymes
Growth
capreomycidine

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Stereocontrolled Total Synthesis of Muraymycin D1 Having a Dual Mode of Action against Mycobacterium tuberculosis. / Mitachi, Katsuhiko; Aleiwi, Bilal A.; Schneider, Christopher M.; Siricilla, Shajila; Kurosu, Michio.

In: Journal of the American Chemical Society, Vol. 138, No. 39, 05.10.2016, p. 12975-12980.

Research output: Contribution to journalArticle

Mitachi, Katsuhiko ; Aleiwi, Bilal A. ; Schneider, Christopher M. ; Siricilla, Shajila ; Kurosu, Michio. / Stereocontrolled Total Synthesis of Muraymycin D1 Having a Dual Mode of Action against Mycobacterium tuberculosis. In: Journal of the American Chemical Society. 2016 ; Vol. 138, No. 39. pp. 12975-12980.
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