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），我们以4-环戊烯-1，3-二醇的单乙酸酯为起始原料，成功地合成了新的前列腺素2-（5，6-环氧异前列烷）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）研究了晚香玉酸、Δ^2-OPC-8：0和OPC-6：0的合成。这些是植物中亚麻酸级联的代谢物。在晚香玉酸的合成中，在环戊烷环上的顺式取向的两个侧链不发生异构化的情况下，侧链末端位置的羟基的保护基应该被脱保护。我们发现在MgBr_2存在下，THP保护基被除去，而没有发生异构化。（2）将选择性地安装到单乙酸酯上的烯基试剂应用于单乙酸环己烯酯。虽然在原始条件下的试剂确实提供了混合物，但发现在TMEDA存在下的锌试剂相对于反式S^2_N'异构体区域选择性地提供了S^2_N-型产物。作为该反应的应用，成功地合成了大麻二酚。（3）由炔丙基格氏试剂和CuCN衍生的炔丙基铜试剂与单乙酸酯反应，区域选择性地生成S^2_N型产物，并转化为合成2-（5，6-环氧异前列烷）磷酰胆碱和Δ^ -PGJ_2的中间体<12>。（4）单乙酸根与丙二酸根阴离子的S^2_N型产物成功地转化为吲哚和异喹啉生物碱。

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.