Development and Application of the Asymmetric Synthesis Using Reactive Acetals

对O，O-， O，S-和N，S-缩醛等反应性缩醛的不对称合成的发展和应用进行了广泛的研究。针对O，O-缩醛类化合物的化学性质，提出了两种脱对称方法：1)以3-内苯基-2-外甲基-5-降冰片烯-2-甲醛为原料，通过分子内卤醚化反应与中位1,2- 1,3- 1,4-二醇进行中位1,2- 1,3- 1,4-二醇的不对称化反应；2)以乙氧基乙烯酯为原料，脂肪酶催化不对称酯转移反应，实现了α -对称1,3- 1 -二醇的不对称化，形成了不对称的季碳中心。方法二应用于抗肿瘤抗生素弗雷迪霉素A abcde类似物的两个对映体的不对称合成。在O， s -缩醛的化学应用方面，研究了醌单O， s -缩醛的应用。通过醌单o、s缩醛与硅烯醇醚或富电子芳烃的反应，开发了一种新的温和高效的磺化反应。另一方面，芳香亲核试剂SN2′攻击醌单o， s -缩醛的β位形成碳-碳键。最后通过醌单o， s -缩醛的修饰实现了上述两条途径的控制。在化学方面，利用N， s-缩醛，合成了抗肿瘤海洋生物碱硫交联核的合成研究。利用高价碘试剂构建螺旋环体系，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discorhabdin 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.