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. 2016 Oct 5;138(39):12975-12980.
doi: 10.1021/jacs.6b07395. Epub 2016 Sep 26.

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

Katsuhiko Mitachi  1 , Bilal A Aleiwi  1 , Christopher M Schneider  1 , Shajila Siricilla  1 , Michio Kurosu  1
Affiliations

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

Katsuhiko Mitachi et al. J Am Chem Soc. .

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).

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Conflict of interest statement

Notes The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Structures of representative muraymycins
Scheme 1
Scheme 1
Retrosynthetic analysis of muraymycin D1
Scheme 2
Scheme 2
Synthesis of the left-half segment
Scheme 3
Scheme 3
Synthesis of the right-half segment
Scheme 4
Scheme 4
Synthesis of muraymycin D1 and its amide analogs
See this image and copyright information in PMC

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