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

利用环戊烷环上碳链安装反应合成前列腺素和生物碱

基本信息

批准号：
16550091
负责人：
KOBAYASHI Yuichi
金额：
$ 2.37万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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.

近两年（2004年、2005年），我们成功合成了新型前列腺素类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））从 4-环戊烯-1,3-二醇的单乙酸酯开始，基于这些结果，我们研究了以下内容。 (1)研究了马铃薯酸、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产物，在马铃薯酸的合成中具有保护作用。我们发现，侧链末端的羟基基团应该被脱保护，而环戊烷环上的两个顺式侧链不会发生异构化。在MgBr_2存在下去除THP保护基，不发生异构化。(2)将选择性安装到单乙酸酯上的烯基试剂应用于环己烯基单乙酸酯，而在原始条件下试剂确实提供了混合物，而在锌试剂存在下。发现 TMEDA 可以区域选择性地提供 S^2_N 型产物，而不是反 S^2_N' 异构体作为该应用。 (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，区域选择性地得到S^2_N型产物，并将该产物转化为合成2-(5 ,6-环氧异前列烷)磷酸胆碱和Δ^<12>-PGJ_2。(4)S^2_N型单乙酸盐与丙二酸阴离子的产物成功转化为吲哚和异喹啉生物碱。

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Moder Organinickel Chemistry, Ed by Y.Tamaru

现代有机镍化学，Y.Tamaru 编

DOI：
发表时间：
2005
期刊：
影响因子：
0
作者：
K.Sekiguchi;M.Atobe;T.Fuchigami;森敦紀;宮田俊介;T.Fuchigami;H.P.Acharya;Timothy M.Boller;T.Sanada;Takashi Nishikata;T.Fuchigami;Y.Kobayashi
通讯作者：
Y.Kobayashi

Synthesis of Phosphorylcholines possessing 5,6-or 14,15-Epoxyisoprostane A_2 at sn-2 Position

sn-2 位点具有 5,6-或 14,15-环氧异前列烷 A_2 的磷酰胆碱的合成