Synthesis of (2R; 4R,S)- and (2S; 4R,S)-dimethyldocosanoic acids

2,4-Dimethyldocosanoic acid is a major acyl component of 2,3-di- O -acyl- α , α -trehalose glycolipid antigens isolated from Mycobacterium tuberculosis . Racemic 2,4-dimethyldocosanoic acid has been synthesised and the chiral centre at C-2 resolved as an (R)-(−)-naphthylethylamide. An isomeric mixture of 3,5-dimethylcyclohexan-l-ols was oxidised to isomeric 3,5-dimethylcyclohexan-l-ones. This was subjected to Baeyer-Villiger oxidation to give isomeric 3,5-dimethylcaprolactones. Ring opening under alkaline conditions followed by phase-transfer catalysed esterification gave isomeric methyl 3,5-dimethyl-6-hydroxyhexanoates. Protection of the alcohol with triphenylmethyl chloride followed by lithium aluminium hydride reduction and pyridinium chlorochromate oxidation gave isomeric 3,5-dimethyl-6-triphenylmethyloxyhexanals. Coupling with hexadecyltriphenylphosphonium bromide, followed by trityl deprotection and hydrogenation of the remaining alkene, yielded isomeric 2,4-dimethyldocosanols. Oxidation with pyridinium dichromate in N , N ′-dimethylformamide produced isomeric 2,4-dimethyldocosanoic acids, which were resolved at C-2 as diastereoisomeric (R)-(−)-naphthylethylamides.