Department of Biotechnology, Tokyo Institute of Technology , B-52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan.
J Org Chem. 2017 Feb 17;82(4):2032-2039. doi: 10.1021/acs.joc.6b02870. Epub 2017 Jan 30.
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 EtAlCN 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)PPh] 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.
分辨率 D5（RvD5）是一种具有抗炎活性的二十二碳六烯酸代谢物，但由于其生物利用度低，尚未得到充分研究。通过组装 C1-C10 醛、C11-C13 鏻盐和 C14-C22 醛砌块，开发了一种光学活性 RvD5 的合成途径。醛片段通过相应的外消旋（E）-1-TMS-1-烯-3-醇的 Sharpless 不对称环氧化反应制备，然后用 EtAlCN 反应，DIBAL 还原（E）-1-氰基-1-烯-3-醇衍生物的 TBS 醚。C14-C22 醛通过 Wittig 反应与 C11-C13 片段（即[TBSO（CH）PPh] Br）相连。所得 C11-C22 中间体转化为磷盐，通过 Wittig 反应将其与 C1-C10 醛连接，得到 RvD5 的结构。
