The synthesis of one enantiomer of the α-methyl-trans-cyclopropane unit of mycolic acids

Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern

“…Here, we addressed this problem by studying the role in airway immune responses of the MA oxygenation class, defined by the distal meromycolic moiety, and the proximal cyclopropane stereochemical configuration. This was made possible because of recent advances in the chemical synthesis of single M. tuberculosis MAs 47–58.…”

The synthesis of single enantiomers of mycobacterial ketomycolic acids containing cis-cyclopropanes

“…The combined organic layers were dried and evaporated. Chromatography eluting with petrol/ether (5:1, 3:1, then 1:1) gave a colourless oil, (8R,9R)-8-(tert-butyldimethylsilanyloxy)-9-methyl heptacosan-1-ol (2.7 g, 86%), ½a 23 3.1.6. (8S,9S)-8-(tert-Butyldimethylsilanyloxy)-9-methylheptacosanal 11.…”

“…The residue was dissolved in petrol (200 ml) and filtered through silica washed with petrol (50 ml). The silica was washed with petrol/ether (1:1, 150 ml) and the solvent was evaporated to give a colourless oil, 2,2-dimethylpropionic acid 10-bromo-decyl ester ( [21][22][23] (1.2 g, 3.31 mmol) in dry THF (20 ml) at rt, cooled to À10 C and lithium bis-(tri-methylsilyl) amide (4.9 ml, 5.2 mmol, 1.06 M) was added at À12 to À5 C. After 1.5 h at rt, dichloromethane (60 ml) and satd aq ammonium chloride (50 ml) were added and extracted. The aqueous layer was reextracted with dichloromethane (2Â30 ml), the combined organic layers were washed with water (100 ml), dried and evaporated.…”

“…22 We have also reported the synthesis of meromycolate fragments containing the a-methyl-trans-cyclopropane unit and provided evidence that the relative stereochemistry of methyl and cyclopropane is as shown in 6, and that, at least in the case of wax esters derived by enzymatic Baeyer-Villiger reaction of keto-mycolates, the absolute stereochemistry of this sub-unit is also as shown in 6. 23 If 6 and 7 are produced through a common intermediate derived by adding a methyl group from SAM to a cisalkene, the stereochemistry of the cis-cyclopropane can then be inferred to be as shown in 7. We have briefly reported syntheses of protected ketomycolates containing both a-methyl-trans-and ciscyclopropane fragments, 6 and 7, that can be adjusted to produce a variety of absolute stereochemistries and chain lengths.…”

Synthesis and Biological Aspects of Mycolic Acids: An Important Target AgainstMycobacterium tuberculosis

“…The synthetic strategy used by Baird and coworkers described above to produce the mycolic acid 65 (Fig. 5) also allowed the synthesis of a different fragment of mycolic acids [49]. For example, Baird and coworkers also synthesized an enantiomer α-methyl-trans-cyclopropane unit 93 (Fig.…”