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

Dulayymi, Juma’a R. Al; Baird, Mark S.; Roberts, Evan

doi:10.1039/b209876h

Cited by 41 publications

(17 citation statements)

References 25 publications

(14 reference statements)

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“…We have reported the synthesis of a range of unique mycolic acids corresponding in structure to those reported to be present in mycobacteria (Al Dulayymi et al, 2005Koza and Baird, 2007;Koza et al, 2009aKoza et al, ,b, 2013Al Kremawi et al, 2010, 2014Muzael et al, 2010). We have also reported the synthesis of the corresponding TDMs and TMMs from a range of these single mycolic acids .…”

Section: Introductionmentioning

confidence: 74%

“…Compound 2d matches the chain lengths and absolute stereochemistry of a trans-cyclopropane mycolic acid of M. tuberculosis (Koza et al, 2009b(Koza et al, , 2013 except that the position adjacent to the ketone is a mixture of epimers. Compound 2e represents the expected absolute stereochemistry of the major a-mycolic of M. tuberculosis (Al Dulayymi et al, 2005), while 2f has the opposite absolute stereochemistry at each cyclopropane (Maza-Iglesias, 2010) (Fig. 1).…”

Section: Resultsmentioning

confidence: 97%

“…above, cesium hydrogen carbonate (70.0 mg, 0.36 mmol), mycolic acid 2e (50 mg, 0.04 mmol) (AlDulayymi et al, 2005) in THF and DMF (1:1, 2.4 mL) and glucopyranoside 1 (36 mg, 0.04 mmol) gave a semi-solid, benzyl 2,3,4-tri-O-benzyl-6-O-[(R)-2-((R)-1-hydroxy-12-((1S,2R)-2-(14-((1S,2R)-2-eicosylcyclopropyl)tetradecyl)-cyclopropyl)dodecyl)hexacosanoyl]-b-D-glucopyranoside 3e (44 mg, 68%),…”

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confidence: 99%

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Glucose monomycolates based on single synthetic mycolic acids

Sahb

Dulayymi

Baird

2015

Chemistry and Physics of Lipids

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Section: Introductionmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 97%

mentioning

confidence: 99%

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Glucose monomycolates based on single synthetic mycolic acids

Sahb

Dulayymi

Baird

2015

Chemistry and Physics of Lipids

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“…For these reasons, extensive work was done recently in the field of chemical synthesis of mycolic acids. Alpha-mycolates were the first synthetic mycolate reported (25), but the synthesis of methoxy-, keto-, and epoxy-mycolic acids as well as single enantiomers of cis-and trans-alkenes-containing mycolates have also been reported and recently reviewed (26).…”

Section: Structure and Diversity Of Mycolic Acids Mycolic Acid Structmentioning

confidence: 99%

The Molecular Genetics of Mycolic Acid Biosynthesis

Pawełczyk

Kremer²

2014

Microbiol Spectr

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Mycolic acids are major and specific long-chain fatty acids that represent essential components of the Mycobacterium tuberculosis cell envelope. They play a crucial role in the cell wall architecture and impermeability, hence the natural resistance of mycobacteria to most antibiotics, and represent key factors in mycobacterial virulence. Biosynthesis of mycolic acid precursors requires two types of fatty acid synthases (FASs), the eukaryotic-like multifunctional enzyme FAS I and the acyl carrier protein (ACP)-dependent FAS II systems, which consists of a series of discrete mono-functional proteins, each catalyzing one reaction in the pathway. Unlike FAS II synthases of other bacteria, the mycobacterial FAS II is incapable of de novo fatty acid synthesis from acetyl-coenzyme A, but instead elongates medium-chain-length fatty acids previously synthesized by FAS I, leading to meromycolic acids. In addition, mycolic acid subspecies with defined biological properties can be distinguished according to the chemical modifications decorating the meromycolate. Nearly all the genetic components involved in both elongation and functionalization of the meromycolic acid have been identified and are generally clustered in distinct transcriptional units. A large body of information has been generated on the enzymology of the mycolic acid biosynthetic pathway and on their genetic and biochemical/structural characterization as targets of several antitubercular drugs. This chapter is a comprehensive overview of mycolic acid structure, function, and biosynthesis. Special emphasis is given to recent work addressing the regulation of mycolic acid biosynthesis, adding new insights to our understanding of how pathogenic mycobacteria adapt their cell wall composition in response to environmental changes.

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“…The overall molecular structure of mycolic acids has been elucidated in the late 1960s, and several members have been prepared by the group of Baird including two methoxy mycolic acid diastereomers (Figure , 1 c and 1 d ). The complete elucidation of their stereochemistry, however, has so far not been achieved.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis

et al. 2020

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In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters (“cord factor”) form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram‐scale synthesis of four stereo‐isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn‐methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material.

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

Cited by 41 publications

References 25 publications

Glucose monomycolates based on single synthetic mycolic acids

Glucose monomycolates based on single synthetic mycolic acids

The Molecular Genetics of Mycolic Acid Biosynthesis

Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis

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