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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16550091/
• 关键词: Cyclopentene monoacetate; Tuberonic acid; OPC-6 : 0; Cannabidiol; Propargyl; Indol alkaloids; Isoquinoline alkaloids; シクロペンテンモノアセテート; ピペリジンアルカロイド; Δ^<12>-PGJ_2; 5,6-エポキシイソプロスタンA_2ホスホコリン; キニーネ; アリル化; 4-シクロペンテン-1,3-ジオール; モノアセテート; 有機合成; Δ^<12

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.

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反应的代谢物。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。

项目成果

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

• 发表时间: 2005
• 期刊: Tetrahedron Lett. 46
• 作者: H.P.Acharya;Y.Kobayashi
• 通讯作者: Y.Kobayashi

Aryl-and Alkenyllithium Preparations and Copper-catalyzed Reaction between the Derived Magnesium Reagents and Monoacetate

芳基和烯基锂的制备以及衍生的镁试剂与单乙酸盐之间的铜催化反应

• 发表时间: 2005
• 期刊: Org.Lett. (印刷中)
• 作者: S.Miyata;H.Yamamura;Y.Inai;R.Tanaka;M.Yamakoshi;M.Kawai;K.Nakata
• 通讯作者: K.Nakata

Highly efficient total synthesis of Δ12-PGJ2, 15-deoxy-Δ12,14-PGJ2, and their analogues

• DOI: 10.1016/j.tet.2006.01.051
• 发表时间: 2006-04-03
• 期刊: TETRAHEDRON
• 影响因子: 2.1
• 作者: Acharya, HP;Kobayashi, Y
• 通讯作者: Kobayashi, Y

Moder Organinickel Chemistry, Ed by Y.Tamaru

现代有机镍化学，Y.Tamaru 编

• 发表时间: 2005
• 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 Cannabidiols via Alkenylation of Cyclohexenyl Monoacetate

单乙酸环己烯酯烯基化合成大麻二酚

• 发表时间: 2006
• 期刊: Org. Lett. 8
• 作者: Y.Kobayashi;A.Takeuchi;Y.-G.Wang
• 通讯作者: Y.-G.Wang