Catalytic asymmetric synthesis of phthioceranic acid, a heptamethyl-branched acid from Mycobacterium tuberculosis.

The first total synthesis of phthioceranic acid (1) has been achieved by an iterative catalytic asymmetric 1,4-addition protocol. This method provides a robust and high-yielding route for the preparation of 1,3-oligomethyl (deoxypropionate) arrays. After the desired number of methyl groups has been introduced, these arrays can be further functionalized at both ends to polymethyl-substituted lipids such as phthioceranic acid, a heptamethyl-branched fatty acid from the virulence factor Sulfolipid-I (2), found in Mycobacterium tuberculosis.