Studies on the development of new, short, and practical synthetic methods for the synthesis of isocarbacyclin

异卡巴环素合成新、短、实用的合成方法开发研究

• 批准号: 05453129
• 负责人: SAITO Seiki
• 金额: $ 4.74万
• 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 (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453129/
• 关键词: isocarbacyclin; Claisen-en sequence; phenyl vinyl sulfoxide; vinly ether formation; (4S)-4-OH-cyclopentenone; chiral homoallylic alcohol; acylsilane as COOH; アシルシラン; 分子内環化; 光学活性4-TBSO-シクロペンテノン; 隣接ジオールコントローラー; 連続クライゼン-エン反応; 鏡像体区別反応; 速度分割; 4塩化

This research has established a novel, short-step, convergent, and practical method for the synthesis of isocarbacyclin featuring a one-pot, three-step process involving vinyl ether formation, Claisen rearrangement, and en reaction to give bicyclo [3.3.1]-backbone, which is not relying on any previous idea in this field that is principally the same as that for prostaglandin synthesis. The new method provided in this research can construct cyclopentenone framework bearing the homoallylic omega-chain longer by one-carbon at first followed by the introduction of the alpha-chain shorter by two-carbon to furnish the precursor for the bicyclo [3.3.1]-backbone. The method required (4S)-4-(O-tert-butyldimethylsilyl)-cyclopent-2-en-1-one as an important starting chiral compound, the antipode of which has been well-known starting material in PG synthesis. In other words, therefore, (4S)-isomer is given significant value which has not been experienced so far.A chiral synthon corresponding to the homoallylic omega-chain has been synthesized efficiently from (S)-1,2-(O-isopropylidene) glycerol in twenty-gram scale and 80-95% yield for each step through a series of routine reactions (7 steps).A precursor for the bicyclo [3.3.1]-backbone to be submitted to the one-pot, three-step process can be provided from an allylic tert-alcohol by vinyl ether formation. We hoped that a reaction to be used in this transformation should be free from mercury salts for some reasons and, after several attempts, has succeeded in developing a new, general method for the synthesis of vinyl ether from various allylic alcohols including tert-versions.

本研究建立了一种新的、短步骤的、收敛的、实用的合成异碳环素的方法，该方法具有一锅法、三步过程，包括乙烯基醚形成、Claisen重排和en反应，以得到双环[3.3.1]-骨架，该方法不依赖于该领域中的任何先前思想，其原理与前列腺素的合成相同。本研究提供的新方法可以首先构建带有长一个碳的同烯丙基ω链的环戊烯酮骨架，然后引入短两个碳的α链，以提供双环[3.3.1]骨架的前体。该方法需要（4S）-4-（O-叔丁基二甲基硅基）-环戊二烯-2-烯-1-酮作为重要的起始手性化合物，其对映体是PG合成中已知的起始原料。从（S）-1，2-通过一系列常规反应（7步），以20克规模制备（O-异亚丙基）甘油，每步产率为80-95%。可通过乙烯基醚的形成由烯丙基叔醇提供待进行一锅三步法的主链。由于某些原因，我们希望在这种转化中使用的反应应该不含汞盐，经过几次尝试，我们成功地开发了一种新的、通用的方法，用于从各种烯丙醇（包括叔醇）合成乙烯基醚。

项目成果

Tadakatsu Mandai, Shin-ichi Matsumoto, Makoto Kohama, Mikio Kawaada, Jiro Tsuji, Seiki Saito, Toshio Moriwake: "A New Highly Efficient Synthetic Method for Isocarbacyclin Based on the Tandem Claisen Rearrangement and Ena Reaction" J.Org.Chem.55. 5671-5673

Tadakatsu Mandai、Shin-ichi Matsumoto、Makoto Kohama、Mikio Kawaada、Jiro Tsuji、Seiki Saito、Toshio Moriwake：“基于串联 Claisen 重排和 Ena 反应的异卡巴环素新型高效合成方法”J.Org.Chem.55。

Tadakatsu Mandai, Jiro Tsuji, Yoshikazu Tsujiguchi, Seiki Saito: "A Novel Route to Cross-Conjugated 4-Oxo-5-alkylidene-2-cyclopentanecarboxylates by Pd (0)-Catalyzed Vicinal Carbonylation of 4-En-2-ynyl Carbonates" J.Am.Chem.Soc.115. 5865-5866 (1993)

Tadakatsu Mandai、Jiro Tsuji、Yoshikazu Tsujiguchi、Seiki Saito：“通过 Pd (0) 催化 4-En-2-ynyl 碳酸酯的邻位羰基化形成交叉共轭 4-Oxo-5-亚烷基-2-环戊烷甲酸酯的新路线”

Seiki Saito, Tetsuya Hara, Kazuhito Naka, Tetsushi Hayashi, Toshio Moriwake: "Enantioselective synthesis of Fundtionalized Cyclopentenone and Alkylidenecyclopentane Derivatives from Acyclic Bisallylic Diol Framework" Synlett. 241-242 (1992)

Seiki Saito、Tetsuya Hara、Kazuhito Naka、Tetsushi Hayashi、Toshio Moriwake：“从无环双烯丙基二醇框架中对映选择性合成基础环戊烯酮和亚烷基环戊烷衍生物”Synlett。

Tadakatsu Mandai and Seiki Saito: "A Novel Route to Cross-Conjugated 4-Oxo-5-alkylidene-2-cyclopentenecarboxylates by Pd(0)-Catalyzed Vicinal Carbonylation of 4-En-2-ynyl Carbonates" The Journal of the American Chemical Society. 115. 5865-5866 (1993)

Tadakatsu Mandai 和 Seiki Saito：“通过 Pd(0) 催化 4-En-2-ynyl 碳酸酯的邻位羰基化形成交叉共轭 4-Oxo-5-alkidene-2-cyclopentenecarboxylates 的新路线” 美国化学杂志

Seiki Saito,Toshihide Yamamoto,Masanobu Matsuoka,Toshio Moriwake: "Tandem Dianionic Dioxy-Cope Rearrangement and Aldol Condensation. A Single-Pot Enantioselective Route to Trans-3,4-disubstituted 2-Formylcyclopentene from Acyclic Bisallylic Compounds" Syn

Seiki Saito、Toshihide Yamamoto、Masanobu Matsuoka、Toshio Moriwake：“串联双阴离子二氧-Cope 重排和羟醛缩合。从无环双烯丙基化合物合成反式 3,4-二取代 2-甲酰基环戊烯的单锅对映选择性路线”