Department of Biotechnology, Tokyo Institute of Technology, B-52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan.
Org Biomol Chem. 2019 Feb 20;17(8):2212-2222. doi: 10.1039/c8ob03128b.
We studied the synthesis of RvD1, a pro-resolving mediator. The intermediate containing vic-diol and enal functional groups was prepared via the oxidation of the γ,δ-epoxy alcohol followed by the epoxide ring opening in one pot. The C11-aldehyde in the resulting enal was converted to the trans iodo-olefin by reaction with TMSC(N2)Li and subsequent hydrozirconation using in situ generated Cp2Zr(H)Cl followed by iodination. The trans enynyl alcohol was synthesized by the reaction of the TMS-containing epoxy alcohol with lithium TMS-acetylide. Finally, two fragments were joined by the Sonogashira coupling, and the triple bond was reduced to afford RvD1 stereoselectively.
我们研究了 RvD1（一种促分解介质）的合成。通过一步法氧化γ,δ-环氧醇并随后开环，制备了含有偕二醇和烯醛官能团的中间体。用 TMSC（N2）Li 与生成的烯醛中的 C11-醛反应，随后用原位生成的 Cp2Zr（H）Cl 进行氢化锆化，再进行碘化，将 C11-醛转化为反式碘代烯烃。通过含 TMS 的环氧醇与锂 TMS-丙炔反应合成了反式烯炔醇。最后，通过 Sonogashira 偶联将两个片段连接起来，并将三键还原，立体选择性地得到 RvD1。
