The synthesis of a single enantiomer of a major α-mycolic acid of M. tuberculosis

Mycolic acids constitute the waxy layer of the outer cell wall of Mycobacterium spp and a few other genera. They are diverse in structure, providing a unique chromatographic foot-print for almost each of the more than seventy Mycobacterium species. Although mainly esterified to cell wall arabinogalactan, trehalose or glucose, some free mycolic acid is secreted during in vitro growth of M. tuberculosis. In M. tuberculosis, alpha-, keto-and methoxy-mycolic acids are the main classes, each differing in their ability to attract neutrophils, induce foamy macrophages or adopt an antigenic structure for antibody recognition. Of interest is their particular relationship to cholesterol, discovered by their ability to attract cholesterol, to bind Amphotericin B or to be recognised by monoclonal antibodies that cross-react with cholesterol. The structural elements that determine this diverse functionality include the carboxylic acid in the mycolic motif, as well as the nature and stereochemistry of the two functional groups in the merochain. The functional diversity of mycolic acid classes implies that much information may be contained in the selective expression and secretion of mycolic acids to establish tuberculosis after infection of the host. Their cholesteroid nature may relate to how they utilize host cholesterol for their persistent survival.

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“…6) [64]. Since that time, all four possible diastereomers of this di-cis-cyclopropane-MA have been synthesised.…”

Section: Synthetic Mycolic Acidsmentioning

confidence: 99%

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

Verschoor

Baird

Grooten

2012

Progress in Lipid Research

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“…The stereochemistry of the proximal carbon and that of the distal carbon of the cis-cyclopropyl group have been determined to be R and S, respectively, according to the knowedge that the cis-cyclopropyl group is derived from the same biosynthetic intermediate of the known stereochemistry (Al Dulayymi et al, 2005). The absolute configurations of the hydroxy-bearing carbon and the carboxyl-bearing carbon in -CH 2 -CH(COOH)-CH(OH)-CH 2 -are both R as reported (Asselineau & Asselineau, 1966;Tocanne & Asselineau, 1968) and as demonstrated by us by easy preparation of its stable chair form acetonide by reduction of MA methyl ester and subsequent acetonide formation (yield 74%).…”

Section: Structural Features Of Representative Mycolic Acid Samplesmentioning

confidence: 99%

Characteristic Conformational Behaviors of Representative Mycolic Acids in the Interfacial Monolayer

Villeneuve¹

2012

Understanding Tuberculosis - Deciphering the Secret Life of the Bacilli

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“…Natural MA mixture was isolated and single synthetic MAs synthesized as previously described (16,(36)(37)(38). The single MAs used for in vivo murine treatment in this study all contained cis-cyclopropanation, referring to the orientation of the proximal cyclopropane.…”

Section: Masmentioning

confidence: 99%

Mycolates of Mycobacterium tuberculosis modulate the flow of cholesterol for bacillary proliferation in murine macrophages

Vermeulen

Baird

Al-Dulayymi

et al. 2017

Journal of Lipid Research

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The synthesis of a single enantiomer of a major α-mycolic acid of M. tuberculosis

Cited by 73 publications

References 46 publications

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis

Characteristic Conformational Behaviors of Representative Mycolic Acids in the Interfacial Monolayer

Mycolates of Mycobacterium tuberculosis modulate the flow of cholesterol for bacillary proliferation in murine macrophages

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