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 Et 2 AlCN 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(CH 2 ) 3 PPh 3 ] + 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.