Sato Y, Taknioto M, Mori M
Graduate School of Pharmaceuitical Sciences, Hokkaido University, Sapporo, Japan.
Chem Pharm Bull (Tokyo). 2000 Nov;48(11):1753-60. doi: 10.1248/cpb.48.1753.
Total synthesis of prostaglandin F2alpha utilizing a nickel(0)-catalyzed cyclization of 1,3-diene and tethered aldehyde was achieved. The cyclization proceeded via a transmetalation of nickelacycle with diisobutylaluminum acetylacetonate (iBu2-ALAC). Thus, the reaction of 19, having a side chain corresponding to the alpha-chain in PGF2alpha with Ni(cod)2 (10 mol %), PPh3 (20 mol %), and 1,3-cyclohexadiene (25 mol %) in the presence of iBu2-ALAC (1.5 eq) proceeded stereoselectively to give the cyclized product 26 in 54% yield. During the cyclization of 19, the Z-olefin at C-5 in the side chain completely retained its geometry, and the four contiguous chiral carbon centers in PGF2alpha were stereoselectively constructed. Transformation of the key intermediate 19 into PGF2alpha was successfully achieved.
实现了利用镍（0）催化的1,3 - 二烯与连接醛的环化反应全合成前列腺素F2α。环化反应通过镍杂环与二异丁基铝乙酰丙酮（iBu2 - ALAC）的转金属化进行。因此，在iBu2 - ALAC（1.5当量）存在下，使具有与PGF2α中α链相对应侧链的19与Ni（cod）2（10摩尔％）、PPh3（20摩尔％）和1,3 - 环己二烯（25摩尔％）反应，立体选择性地进行，以54％的产率得到环化产物26。在19的环化过程中，侧链中C - 5处的Z - 烯烃完全保留了其几何构型，并且立体选择性地构建了PGF2α中四个相邻的手性碳中心。关键中间体19成功转化为PGF2α。
