Construction of Chiral Building Blocks through Enantioselective Protonation

通过对映选择性质子化构建手性结构单元

• 批准号: 63430024
• 负责人: FUJI Kaoru
• 金额: $ 1.98万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63430024/
• 关键词: Asymmetric Synthesis; Enantioselective Reaction; Protonation; Addition-Elimination; Optical Resolution; Indole Alkaloid; Chiral Synthesis; ニトロオレフィン; インドールアルカロイド; アスピドスペルミジン

We had previously succeeded in preparing a chiral building block, (S)-3-(4gamma-butyrolactone)-propionic acid (1), by an enantioselective protonation with (1S)-10-camphor-sulfonic acid onto disodium 4-hydroxypimelate. Optically active oudenone, isolated from Oudemansiella radicata, was synthesized from 1. Oudenone has significant hypotensive activity against spontaneously hypertensive rats due to inhibitions of tyrosine hydroxylase. Two-step reduction of 1 afforded (S)-4-heptanolide, which was transformed into a methyloxonium species by the reaction with magic methyl. Reaction of the methyloxonium species with an enorate of 1,3-pentane-dione gave optically active oudenone. A chiral building block 1 was utilized for the syntheses of pheromones such as 4-hexanolide, eldanolide, 4-dodecanolide.Another chiral 6-membered lactone prepared through addition-elimination process was successfully used for the chiral synthesis of optically active podocarpic acid. Since podocarpic acid has been converted into six diterpenoids including taxodione, which has been claimed to possess anti-tumor activity, chiral synthesis of podocarpic acid constitutes a formal total synthesis of these six diterpenoids in optically active form.

我们以前成功地制备了一个手性结构单元，（S）-3-（4 γ-丁内酯）-丙酸（1），通过对映选择性质子化与（1 S）-10-乙酰基-磺酸上的4-羟基庚二酸二钠。从长根奥德蘑（Oudemansiellaradicata）中分离得到光学活性的乌地酮。乌地酮对自发性高血压大鼠有明显的降压作用，其机制可能与抑制酪氨酸羟化酶有关。1经两步还原得到（S）-4-庚烷并与幻甲基反应生成甲基氧鎓。甲基氧鎓与1，3-戊二酮的双酯反应得到光学活性的乌地酮。利用手性结构单元1合成了4-己内酯、依丹酮、4-十二烷酮等信息素，通过加成-消除反应合成了手性六元内酯，成功地合成了光学活性的罗汉果酸。由于罗汉果酸已被转化为六个二萜类化合物，包括紫杉二酮，已被声称具有抗肿瘤活性，罗汉果酸的手性合成构成了这六个二萜类化合物的光学活性形式的正式全合成。

项目成果

M.Ochiai,M.Kunishima,K.Fuji,and Y.Nagao: "Conjugate Addition of Acyloxy Groups to Alkylphenyl-Iodonium Tetrafluoroborates under Both Basic and Acidic Conditions.Synthesis of alpha-Acyloxy Ketones." J.Org.Chem.54. 4038-4041 (1989)

M.Ochiai、M.Kunishima、K.Fuji 和 Y.Nagao：“在碱性和酸性条件下将酰氧基基团与烷基苯基碘鎓四氟硼酸盐共轭加成。α-酰氧基酮的合成”。

K.Fuji,M.Node,F.Tanaka,and S.Hosoi: "Binaphthol as a Chiral Auxiliary.Asymmetric Alkylation of Arylacetic Acid" Tetrahedron Lett.30. 2825-2828 (1989)

K.Fuji、M.Node、F.Tanaka 和 S.Hosoi：“联萘酚作为手性助剂。芳基乙酸的不对称烷基化”四面体 Lett.30。

M.Ochiai,M.Kunishima,K.Fuji,Y.Nagao,and M.Shiro: "Synthesis,Structure,and Self-Oxidation of Alkynyl(phenyl)iodonium Periodates." Chem.Pharm.Bull.37. 1948-1950 (1989)

M.Ochiai、M.Kunishima、K.Fuji、Y.Nagao 和 M.Shiro：“炔基（苯基）碘鎓高碘酸盐的合成、结构和自氧化”。

Z.-Q. Wang, M. Node, F.-M. Xu, H.-P. Hu, and K. Fuji: "Terpenoids. LIV. The Structures of Rabdoinflexins A and B, New Diterpenois form Rabdosia inflexa (THUNB.) HARA" Chem. Pharm. Bull., 1989, 37, 2683.

Z.-Q。

K. Fuji, M. Node, F. Tanaka, and S. Hosoi: "Binaphthol as a Chiral Auxiliary. Asymmetric Alkylation of Arylacetic Acid." Tetrahedron Lett., 1989, 30, 2825.

K. Fuji、M. Node、F. Tanaka 和 S. Hosoi：“联萘酚作为手性助剂。芳基乙酸的不对称烷基化。”