Synthesis of Prostaglandins and Alkaloids using Reactions for Installation of Carbon Chain on the Cyclopentane Ring

在过去的两年中（2004,2005），我们成功地从4-环戊烯-1,3-二醇的单乙酸酯开始合成了新的前列腺素- 2-（5,6-环氧异前列腺素）磷酰胆碱和Δ^<12>-前列腺素J_2 （Δ^<12>- pgj_2）。基于这些结果，我们进行了以下研究。(1)研究了结核酸Δ^2- opc - 8.0和opc - 6.0的合成。这些是植物中亚麻酸级联反应的代谢物。在合成tuberonic酸时，环戊烷环上顺式的两个侧链在不异构化的情况下，侧端羟基的保护基团要去保护。我们发现THP保护基团在MgBr_2存在下被去除而没有异构化。(2)将选择性安装在单乙酸酯上的烯基试剂应用于单乙酸环己烯基。虽然在原始条件下的试剂确实产生了混合物，但发现锌试剂在TMEDA存在下选择性地产生S^2_N型产物区域，而不是抗S^2_N'异构体。作为该反应的应用，成功地合成了大麻二酚。(3)丙炔铜试剂由丙炔格氏试剂和CuCN与单乙酸酯反应得到，选择性产生S^ 2_n型产物，产物转化为合成2-（5,6-环氧异前列腺烷）磷胆碱和Δ^<12>- pgj_2的中间体。(4)单乙酸酯与丙二酸阴离子的S^ 2_n型产物成功转化为吲哚类和异喹啉类生物碱。

In the past two years (2004, 2005), we have succeeded in synthesis of 2-(5,6-epoxyisoprostane)phosphoryl choline, a new prostanoid, and Δ^<12>-prostaglandin J_2 (Δ^<12>-PGJ_2) starting from the monoacetate of 4-cyclopentene-1,3-diol. Based on these results we have investigated the following researches.(1)Synthesis of tuberonic acid, Δ^2-OPC-8 : 0, and OPC-6 : 0 has been studied. These are metabolites of the linolenic acid cascade in plants. In the synthesis of tuberonic acid, a protective group for the hydroxyl group at the terminal position of the side should be deprotected without isomerization of the cis-orientated two side chains on the cyclopentane ring. We found that THP protective group was removed in the presence of MgBr_2 without the isomerization.(2)Alkenyl reagents which are selectively installed to the monoacetate were applied to cyclohexenyl monoacetate. While the reagents under the original conditions did afford a mixture, the zinc reagents in the presence of TMEDA was found to afford the S^2_N-type product regioselectively over the anti S^2_N' isomer. As an application of this reaction, cannabidiol was successfully synthesized.(3)Propargyl copper reagent derived from the propargyl Grignard reagent and CuCN upon reaction with the monoacetate afforded the S^2_N-type product regioselectively and the product was transformed to the intermediates for synthesis of 2-(5,6-epoxyisoprostane)phosphorylcholine and Δ^<12>-PGJ_2.(4)The S^2_N-type product of the monoacetate with the malonate anion was successfully transformed to the indol and isoquinoline alkaloids.