Development of Novel Carbon-Carbon Bond Fragmentation Reaction by Means of Samarium Diiodide and Its Application to the Synthesis of Physiologically Active Compounds

二碘化钐新型碳-碳键断裂反应的进展及其在生理活性化合物合成中的应用

• 批准号: 06672118
• 负责人: HONDA Toshio
• 金额: $ 1.09万
• 依托单位: Laboratory of Synthetic Organic Chemistry, Institute of Medicinal Chemistry, Hoshi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672118/
• 关键词: Samarium diiodide; Fragnentation Reaction; (-)-Oudemansin A; (+)-Eldanolide; (-)-cis-Whisky lactone; Necic acid; Piperidine alkaloid; Pyrrolizidind allaloid; 抗腫瘍性ステロイド; 立体選択的キラル合成

Development of the chemistry of samarium (II) iodide has been of continuing interest in organic synthesis because of its quite unique and useful properties, such as poweful reducing ability in addition to the chemoselectivity. Although the variety of useful transformation using samarium diiodide are investigated to date, little attention has focused on the fragmentatin reaction. We have there fore attempted to develop an efficient method for the reductive carbon-carbon bond cleavage reaction by utilization of samarium diiodide and found that the reaction of gamma-halo carbonyl compounds with samarium diiodide afforded the regioselective fragmentation reaction products in high yields. When this reaction was applied to the gamma-helo ester, derived from monoterpene carvone, the useful chiral building block could be prepared.Using the chiral building block as a starting material, the synthesis of (-)-oudemansin A, an antitumour compound, was achieved stereoselectively. Moreover this synthetic strategy was applied to the efficinet synthesis of gamma-lactonic compounds, such as cis-whisky lactone and eldanolide. The biologically interesting piperidine alkaloids, (-)-anhydronupharamine, (-)-nupharamine, (-)-nuphenine and (+)-3-epinupharamine, and pyrrolizidine alkaloid, (-)-heliotidane, were also synthesized in optically pure forms. Finally stereoselective synthetic procedures for the necic acid components of macropyrrolizidine alkaloids, crobarbatic acid andintegerrinecic acid lactone were established by utilization of this fragmentation reaction as a key step.These results clearly indicated that the newly developed samarium diiodide promoted fragmentation reaction of gamma-halo esters is a useful reaction in the synthesis of various types of physiologically active compounds.

碘化钐的化学发展一直受到有机合成领域的关注，因为它具有非常独特和有用的性质，如强大的还原能力和化学选择性。尽管迄今为止研究了利用二碘化钐进行的各种有用的转化，但对破碎反应的关注很少。因此，我们试图开发一种利用二碘化钐进行还原性碳-碳键裂解反应的有效方法，并发现-halo羰基化合物与二碘化钐的反应可提供高收率的区域选择性裂解反应产物。当将此反应应用于从单萜香芹酮衍生的-helo酯时，可以制备有用的手性构建块。以手性构建块为起始材料，立体选择性地合成了抗肿瘤化合物(-)-oudemansin a。此外，该合成策略还有效地合成了-内酯类化合物，如顺式威士忌内酯和艾尔丹内酯。以光学纯形式合成了具有生物学意义的胡椒碱类生物碱(-)-anhydronupharamine, (-)-nupharamine, (-)-nupharamine, (-)-nuphenine和(+)-3-epinupharamine，以及吡咯利西啶类生物碱(-)-heliotidane。最后以裂解反应为关键步骤，建立了立体选择性合成大吡咯里西啶类生物碱的乙酸组分、巴巴巴拉酸和整合霉素酸内酯的工艺流程。这些结果清楚地表明，新开发的二碘化钐促进γ -halo酯的断裂反应是合成各种生理活性化合物的有用反应。

项目成果

Toshio Honda: "A Concise Enantiospeific Synthesis of Nuphar Piperidine Alkaloids : Total Synthesis of (-)-Anhydronupharamine, (-)-Nupharamine, (-)-Nuphnime and (+)-3-Epinupharamine" J.Chem. Soc., Chem. Commun.499 (1994)

Toshio Honda：“Nuphar 哌啶生物碱的简明对映体合成：(-)-Anhydronupharamine、(-)-Nupharamine、(-)-Nuphnime 和 ( )-3-Epinupharamine 的全合成”J.Chem。

Toshio Hoda: "Chiral Synthsis of a Pyrrolizidine Alkaloid, (-)-Heliotrodane" Heterocycles. 40. 301 (1995)

Toshio Hoda：“吡咯里西啶生物碱、(-)-Heliotrodane”杂环的手性合成。

本多利雄: "Chiral Synthesis of the Necic Acid Components, Crobarbatic Acid and Integerrinecic Acid Lactone" J. Chem. Soc., Perkin Trans. 1. (印刷中).

Toshio Honda：“Necic Acid 成分、Crobarbatic Acid 和 Integerrinecic Acid Lattone 的手性合成”J. Chem. Soc.，Perkin Trans 1。（出版中）。

本多 利雄: "A Concise Enantiospecific Synthesis of Nuphar Piperidine Alkaloids:Total Synthlsis of (-)-Anhydronupharamine,(-)-Niupharamine(-)-Nuphenine and (+)-3-Epinupharamine" J.Chem.Soc.,Chem.Commun.499-500 (1994)

Toshio Honda：“Nuphar 哌啶生物碱的简明对映体特异性合成：(-)-Anhydronupharamine、(-)-Niupharamine(-)-Nuphenine 和 (+)-3-Epinupharamine 的全合成”J.Chem.Soc.、Chem 。通讯499-500 (1994)

本多 利雄: "Chiral Synthesis of a Pyrrolizidine Alkaloid,(-)-Heliotridane" Heterocycles. 40. 301-310 (1995)

Toshio Honda：“吡咯里西啶生物碱，(-)-Heliotridane 的手性合成”杂环。 40. 301-310 (1995)