Development and Application of the Asymmetric Synthesis Using Reactive Acetals

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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.