Development and Application of the Asymmetric Synthesis Using Reactive Acetals

对O，O-，O，S-和N，S-等反应性缩醛的不对称合成进行了广泛的研究。在O，O-缩醛的化学合成中，发展了两种不对称合成方法：1)基于3-endo-phenyl-2-exo-methyl-5-norbornene-2-carboxaldehyde制备的烯缩醛与Meso-1，2-，1，3-和1，4-二醇的分子内卤代醚化反应的关键反应，2)σ对称的1，3-二醇的去对称化反应，通过脂肪酶催化乙氧基乙烯基酯的不对称酯转移反应形成不对称的季碳中心。方法2应用于抗癌药物弗雷德霉素A的ABCDE类似物的两个对映体的不对称合成，在以O，S缩醛为原料的反应中，对苯二酚单O，S缩醛的使用进行了研究。由苯二酮单-O、S缩醛和硅烯醇醚或富电子芳烃反应，开发了一种温和而有效的新的亚磺化反应。另一方面，芳香族亲核试剂Sn2‘对苯二酮单-O、S缩醛的β-位的攻击促进了碳-碳键的形成。在以N，S缩醛为原料的化学合成基础上，进行了抗肿瘤海洋生物碱硫交联核的合成研究。用高价碘试剂构建螺环体系，实现了N，O-缩醛向N，S-缩醛的有效转化。该方法首次应用于不协调素A的全合成。

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.