386. Synthesis of mycolipenic acid

Abstract

The total synthesis of mycolipenic acid has been completed. (+)-2(L): 4(L)-Dimethyldocosanoic acid * (I), an oxidation product of mycolipenic acid which has been previously synthesised, was converted essentially by a route already described for an optically inactive specimen into (+)-2 : 4(L) : 6(L)-trimethyltetracos-2-enoic acid (IV; R = H). The synthetic acid, regarded as the trans-isomer, is found to be identical with mycolipenic acid isolated from tubercle bacilli.

One‐Step Homologation for the Catalytic Asymmetric Synthesis of Deoxypropionates

“…[17,20] Mycolipenic acid 1 was first synthesized and characterized by Polgar et al in 1958 by al engthy route comprising ak inetic resolution. [21] Minnikin andc o-workers synthesized 1 as ar acemate in 1992. [22] Recently,M innaard and Feringa reportedac atalytic asymmetrics ynthesisofm ycolipenic acid 1 by using an iterative three-step homologation procedure involvingC u-catalyzeda symmetricc onjugate addition of MeMgBrt oa,b-unsaturated thioesters (Scheme 1a), which required 14 longest linear steps in 3% overall yield from glycol.…”

“…Mycolipenic acid 1 was first synthesized and characterized by Polgar et al. in 1958 by a lengthy route comprising a kinetic resolution . Minnikin and co‐workers synthesized 1 as a racemate in 1992 .…”

Catalytic Asymmetric Synthesis of Mycolipenic and Mycolipanolic Acid

“…Mycolipenic acid ( 3 ) was first isolated and characterized in the 1950s by Polgar 12,13. The compound was synthesized in 1958 by a lengthy route, comprising a kinetic resolution, which confirmed the stereochemistry to be all‐( S ) and the double bond to have ( E ) stereochemistry 13. Mycolipenic acid has been synthesized as a racemate by Minnikin et al in 1992 9…”

Iterative strategies for the synthesis of deoxypropionates

“…43 The optical rotation of the synthetic material, +16.4 (c = 1.96, CHCl 3 ), matched with that reported in the literature for the natural product isolated from M. tuberculosis (+19). 44,45 For the introduction of the syn-hydroxy-methyl unit in the synthesis of mycolipanolic acid (66), an Evans aldol reaction of the boron enolate of enantiopure oxazolidone 67 with aldehyde 63 was used. 10,46 To prevent over-oxidation or epimerization at the alpha stereocentre, 63 was prepared freshly by oxidation of alcohol 62 employing the NMO/TPAP procedure followed by quick purification over silica (Scheme 16).…”