Total Synthesis of Resolvin D5.

Resolvin D5 (RvD5) is a metabolite of docosahexanoic acid with anti-inflammatory activity that has not yet been thoroughly investigated because of its low biological availability. A synthetic route to optically active RvD5 was developed by assembling the C1-C10 aldehyde, C11-C13 phosphonium salt, and C14-C22 aldehyde building blocks. The aldehyde fragments were prepared by Sharpless asymmetric epoxidation of corresponding racemic (E)-1-TMS-1-alken-3-ols followed by reaction of the TBS ethers of the resulting epoxy alcohols with Et2AlCN and DIBAL reduction of the (E)-1-cyano-1-alken-3-ol derivatives. The C14-C22 aldehyde was connected with the C11-C13 fragment, i.e., [TBSO(CH2)3PPh3]+ Br-, by Wittig reaction. The resulting C11-C22 intermediate was converted to the phosphonium salt, which was attached to the C1-C10 aldehyde by Wittig reaction to yield the structure of RvD5.