Development and Application of the Asymmetric Synthesis Using Reactive Acetals

反应性缩醛不对称合成的研究进展及应用

基本信息

批准号：
12470477
负责人：
KITA Yasuyuki
金额：
$ 8.83万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Development and application of the asymmetric synthesis using reactive acetals such as O,O-, O,S- and N,S-acetals were studied extensively.On the chemistries using O,O-acetals, two desymmetrization method were developed : 1) asymmetrization of meso-1,2-, 1,3-, and 1,4-diols based on a key reaction of an intramolecular haloetherification reaction of the ene acetals prepared from 3-endo-phenyl-2-exo-methyl-5-norbornene-2-carboxaldehyde and meso-1,2-, 1,3-, and 1,4-diols, and 2) desymmetrization of σ-symmetric 1,3-diols leading to the formation of asymmetric quaternary carbon centers by lipase-catalyzed asymmetric ester transfer reactions using ethoxyvinyl esters. Method 2 was applied to the asymmetric synthesis of both enantiomers of ABCDE-analog of fredericamycin A, the antitumor antibiotic.On the chemistries using O,S-acetals, the use of quinone mono-O,S-acetals was studied. New mild and efficient sulfenylation was developed by the reaction of quinone mono-O,S-acetals and silyl enol ethers or electron-riched aromatics. On the other hand, carbon-carbon bond formation was developed by SN2' attack of aromatic nucleophiles to the β-positions of quinone mono-O,S-acetals. Finally the control of the above two routes was achieved by the modification of quinone mono-O,S-acetals.On the chemistries using N,S-acetals, synthetic studies on sulfur cross-linked core of antitumor marine alkaloid, discorhabdins, have been done. Effective transformation of N,O-acetals to N,S-acetals have been achieved after construction of the spiro ring system by hypervalent iodine reagent. This method was applied to the first total synthesis of discorhabdin A.

广泛研究了使用反应性乙烯（例如O，O-，O，S-和N，S-乙齿）的不对称合成的开发和应用。在使用O，O-乙的化学中，开发了两种脱对称方法：1）基于MESO-1,2-，1,3-，1,3-和1,4-diole的MESO-1,2-，1,3-型反应的非对称方法由3-二苯基-2-二甲基-5-甲基-5-苯乙烯-2-羧甲醛和中甲醛和中甲醛和中甲基和1,3-和1,4-二醇和2）脱离σ-对称对称1,3-二醇的去对称，从乙氧乙烯基酯。方法2应用于Fredericamycin A的Abcde-Analog的两种对映异构体的不对称合成，抗毒抗抗生素。使用O，S-acetals的化学物质，使用Quinone Mono-O，S-acetals使用S-acetals。通过奎因酮单OO，S乙酮和甲硅烷基烯醇醚或富含电子的芳香剂的反应，开发了新的轻度和有效的磺苯基化。另一方面，通过芳族核致粉对喹酮单o-O，s-乙的β位置的SN2'攻击碳碳键的形成是开发出来的。最终，通过N，S乙酰基，S乙蛋白，S-acetals，关于抗肿瘤海洋生物碱的硫交联核心，Discororhabdins的硫酮单核，s乙烯，discorhabdins的合成研究，通过N，s乙酸，合成研究来实现上述两种途径的控制。通过高价值碘试剂构建螺旋环系统后，已经实现了n，o乙乙烯的有效转化。该方法应用于Discorhabdin A的第一个总合成。