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

Article abstract of DOI:10.1016/0009-3084(94)90019-1

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.