Development of Highly Versatile C_4-Chiral Building Blocks from L-Malic acid and Their Utilization in Natural Product Syntheses

L-苹果酸高度通用的 C_4-手性结构单元的开发及其在天然产物合成中的应用

• 批准号: 60550613
• 负责人: SAITO Seiki
• 金额: $ 1.34万
• 依托单位: Okayama 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: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60550613/
• 关键词: L-Malic Acid Esters; Selective Reduction; L-Tartaric Acid Esters; Succinate Derivatives; 3,4-Dihydroxybutanoates; 2-Substituted-3,4-dihydroxybutanoates; Isocarbacyclin; Chiral Synthons; リンゴ酸; 酒石酸; 【C_4】-キラルシントン; オクタヒドロナフタレン; コンパクチン; キラル4-ヒドロキ

This research aims at developing highly versatile C_4-chiral synthons from L-malic acid which should enjoy large popularity in natural product syntheses. A newly developed method for selective reduction of alpha-hydroxy esters has provide a number of otherwise inaccessible chiral synthons which constitutes the central strategy in this research. The selective reduction involves, in principle, hydroxy-directed activation of the alpha-ester group and turned out to be applicable to L-tartrate-based derivatives which provided additional diverse chiral synthons. A various types of synthetic intermediates furnished by this reduction bears commonly one ester group and 3,4-dihydroxy functionality. This structural feature promises potent possibilities in a myriad of contexts for organic transformations which follows therefrom because the 3,4-dihydroxy functionality is amenable to selective easy protection and the ester group can be embodied in target molecule if so desired. We have prepared the following compounds of synthetic and biological interests starting from such chiral synthons : gamma-lactone derivative, cis-and trans-2,3-epoxy esters, (S) -glyceraldehyde acetonide, carnitine and unnatural functional alpha-amino acids, beta-lactam derivatives, heterocyclic compounds, octahydronaphthalene derivatives, and cyclopentane derivatives. When coupled with an idea to introduce formyl functionality by Claisen rearrangement, ene-carbacyclization strategy employed in the synthesis of the cyclopentane derivatives has led to a hopeful stage in which an extremely fascinating synthetic work directed toward isocarbacyclin can become available. The synthetic route developed by us should put stress on the point that it constitutes the most short-cut route to isocarbacyclin among those reported so far.

本研究旨在从L-苹果酸出发，开发具有广泛应用前景的C_4手性配体。一种新开发的选择性还原α-羟基酯的方法提供了许多否则难以获得的手性配体，这构成了本研究的中心策略。原则上，选择性还原涉及α-酯基的羟基定向活化，并被证明适用于L-酒石酸酯基衍生物，其提供了额外的不同手性配体。通过这种还原提供的各种类型的合成中间体通常带有一个酯基和3，4-二羟基官能团。这种结构特征在无数的有机转化的背景下保证了潜在的可能性，这是因为3，4-二羟基官能团易于选择性保护，并且如果需要的话，酯基可以包含在靶分子中。我们已经从这些手性化合物出发制备了以下具有合成和生物学意义的化合物：γ-内酯衍生物、顺式和反式-2，3-环氧酯、（S）-甘油醛缩丙酮、肉毒碱和非天然功能性α-氨基酸、β-内酰胺衍生物、杂环化合物、八氢萘衍生物和环戊烷衍生物。当再加上一个想法，引入甲酰基功能的Claisen重排，在环戊烷衍生物的合成中采用的烯-carbacyclization策略，导致了一个充满希望的阶段，其中一个非常迷人的合成工作，针对isocarbacyclin可以成为可用。我们开发的合成路线应该强调的一点是，它构成了最快捷的路线，isocarbacyclin在那些报道至今。

项目成果

T.Mandai, S.Matsumoto, M.Kohama, M.Kawada, J.Tsuji, S.Saito, and T.Moriwake: "A New Highly Efficient Method for Isocarbacyclin Synthesis Based on Tandem Claisen Rearrangement and Ene Reactions" The Journal of Organic Chemistry. 55. 5671-5673 (1990)

T.Mandai、S.Matsumoto、M.Kohama、M.Kawada、J.Tsuji、S.Saito 和 T.Moriwake：“基于串联 Claisen 重排和 Ene 反应的异卡巴环素合成新高效方法”

Seiki Saito;Yuki Nagao;Masahiro Miyazaki;Masami Inaba;Toshio Moriwake: Tetrahedron Letters. 27. 5249-5252 (1986)

斋藤精树；长尾佑树；宫崎正宏；稻叶雅美；森分敏夫：四面体字母。

S.Saito,^* H.Nakajima,M.Inaba,and T.Moriwake^*: "One-pot Transfromation of Azido-group to N-(t-Butoxycarbonyl)amino Group" Tetrahedron Letters. 26. 5309-5312 (1985)

S.Saito、^* H.Nakajima、M.Inaba 和 T.Moriwake^*：“叠氮基到 N-(t-丁氧羰基)氨基的一锅转化”四面体字母。

S.Saito, S.Yamashita, T.Nishikawa, Y.Yokoyama, M.Inaba, and T.Moriwake: "Highly Nucleophilic Tributyltin Azide in Oxirane Ring Cleavage Leading to 1,2-Azido Alcohol" Tetrahedron Letters. 30. 4153-4156 (1989)

S.Saito、S.Yamashita、T.Nishikawa、Y.Yokoyama、M.Inaba 和 T.Moriwake：“环氧乙烷环裂解中的高度亲核三丁基叠氮化锡导致 1,2-叠氮醇”四面体字母。

S.Saito, T.Hasegawa, M.Inaba, R.Nishida, T.Fujii, S.Nomizu, and T.Moriwake: "Combination of Borane-Dimethyl Sulfide Complex with Catalytic Sodium Tetrahydroborate as a Selective Reducing Agent for alpha-Hydroxy Esters. Versatile Chiral Building Block From

S.Saito、T.Hasekawa、M.Inaba、R.Nishida、T.Fujii、S.Nomizu 和 T.Moriwake：“硼烷二甲基硫醚络合物与催化四氢硼酸钠的组合作为 α-羟基的选择性还原剂