The synthesis of single enantiomers of meromycolic acids from mycobacterial wax esters

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

“…CH 3 (CH 2 ) 17 (CH 2 ) 16 For the synthesis of stereoisomers of compound 7, the cis-cyclopropane was introduced as 19 21-23 or its enantiomer. [20][21][22] Condensation of 17 with 19 in a modified Julia-Kocienski reaction, 25 followed by saturation of the derived E/Z alkene mixture using diimide, led to ester 20. Removal of the ester group reductively followed by oxidation of the derived alcohol 21, led to aldehyde 22 (Scheme 7) CH 3 (CH 2 ) 17 (CH 2 (i), (ii) (iii) Scheme 7.…”

“…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.…”

“…19 The stereochemistry was shown to affect host innate immune responses both positively and negatively. We have recently reported the synthesis of an a-mycolate of type 1, 20,21 and of methoxymycolates of type 2 with either absolute stereochemistry at the cis-cyclopropane or a-methyl-bmethoxy fragment. 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.…”

Thiol modified mycolic acids

“…We have already reported the synthesis of mycolic acids with the same structures and chain lengths as the major homologues present in natural mixtures; in each case the molecule has been prepared as a single enantiomer [Al Dulayymi et al, 2003, 2006a. We now report the preparation of four such molecules, in each case modified by the introduction of a thiol substituent at the end of the α-carbon chain of the meromycolate fragment.…”

The synthesis of single enantiomers of trans-alkene-containing mycolic acids

“…9 As part of a study to determine the biological significance of individual MAs and particularly of their stereochemistry, we have reported routes to a-, methoxy-and keto-MAs as single stereoisomers, as well as to related wax esters. [27][28][29][30][31] We now report the first synthesis of type-2 hydroxy-MA 16 (R = R 0 = H) and 18 and the related keto-MA (21).…”