The first syntheses of single enantiomers of the major methoxymycolic acid of Mycobacterium tuberculosis

Abstract

The synthesis of three stereoisomers of a major homologue of the methoxymycolic acids present in Mycobacterium tuberculosis is described. Graphical abstractArticle Outline

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

“…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.…”

Thiol modified mycolic acids

“…Coupling of this aldehyde (19) to the known sulfone (20) [Al Dulayymi, 2007] in the presence of base followed by hydrogenation led to alcohol (21) (Scheme 3). This was converted into the corresponding thioacetate (22); the transformation of alcohol to thioacetate was confirmed by the replacement of a triplet the methylene group adjacent to oxygen at δ H 3.7 with that adjacent to the thioacetate at δ 2.86, and the loss of the corresponding carbon signal at δ C 63.…”

“…As in the case of its diastereomer (24), the methylene group adjacent to sulfur appeared at δ 2.7. The carbons adjacent to sulfur in (24) and (28) and CH(COOH) carbons as seen in the parent methoxymycolic acid with no sulfur substituent on the α-chain [Al Dulayymi, 2007]. There were also signals at δ C 10.9…”

“…(i) Lithium bis(trimethylsilyl)amide (2.17 ml, 2.30 mmol, 1.06 M) was added dropwise to a stirred solution of ester (19) (1.00 g, 1.33 mmol) and tetrazole (25) (1.37 g, 1.53 mmol) [Al Dulayymi, 2007] in dry THF (50 ml) at -10 ˚C. The reaction turned bright yellow and was left to reach r.t. and stirred for 1 hr under nitrogen then quenched with sat.aq.…”

A biomimetic approach to the synthesis of a mycolic acid motif

“…This synthesis of the mycolic acid motif methyl ester 2 represents a novel approach to a key intermediate that has been used to prepare mycolic acids. 11 The use of anti-aldol methodology reduces the number of steps required from six, 11 to two. Prior to the removal of the auxiliary, the diastereomeric products are readily separated giving the desired R,R-product in >98% ee.…”