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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470477/
• 关键词: asymmetric desymmetrization; 3-endo-phenyl-2-exo-methyl-5-norbornene-2-carboxaldehyde; meso- 1,4-diol; ethoxyvinyl esters; lipase-catalyzed asymmetric ester transfer; quinone mono-O,S-acetals; N,S-acetals; discorhabdin A; (R,R)-ヒドロベンゾイン; ノルボルネンアル

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.

对使用O,O-、O,S-和N,S-缩醛等反应性缩醛的不对称合成的开发和应用进行了广泛的研究。在使用O,O-缩醛的化学中，开发了两种不对称化方法：1）基于烯分子内卤醚化反应的关键反应，内消旋1,2-、1,3-和1,4-二醇的不对称化 由3-内型-苯基-2-外型-甲基-5-降冰片烯-2-甲醛和内消旋-1,2-、1,3-和1,4-二醇制备的缩醛，以及2) σ-对称1,3-二醇的去对称化，通过脂肪酶催化的不对称酯转移反应导致形成不对称季碳中心 乙氧基乙烯基酯。方法2应用于抗肿瘤抗生素弗雷德雷霉素A的ABCDE类似物的两种对映体的不对称合成。在使用O,S-缩醛的化学中，研究了醌单-O,S-缩醛的使用。通过醌单-O,S-缩醛与甲硅烷基烯醇醚或富电子芳烃的反应，开发了新的温和高效的磺基化反应。另一方面，碳-碳键的形成是通过芳香族亲核试剂的SN2'攻击醌单-O,S-缩醛的β-位而形成的。最后通过对醌单-O,S-缩醛的修饰实现了对上述两条途径的控制。在N,S-缩醛化学上，对抗肿瘤海洋生物碱Discorhabdins的硫交联核心进行了合成研究。通过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discorhabdin A的全合成。

项目成果

Fujioka, Hiromichi: "Asymmetric Desymmetrization of Saturated and Unsaturated meso-1,2-Diols"Tetrahedron. 56. 10141-10151 (2000)

Fujioka、Hiromichi：“饱和和不饱和内消旋 1,2-二醇的不对称去对称化”四面体。

AKAl, Shuji: "Lipase-Catalyzed Enantioselective Desymmetrization of Prochirai 3, 3-Bis(hydroxymethyl ) oxindoles"Tetrahedron Letters. 42. 7315-7317 (2001)

AKAl，Shuji：“脂肪酶催化的 Prochirai 3, 3-双（羟甲基）羟吲哚的对映选择性去对称化”四面体字母。

Fujioka, Hiromichi: "Optical Resolution of Racemic Norbornene Aldehydes : Kinetically Controlled Intramolecular Haloetherification of Ene Acetals"Tetrahedron Letters. 41. 1829-1832 (2000)

Fujioka，Hiromichi：“外消旋降冰片烯醛的光学拆分：烯缩醛的动力学控制分子内卤醚化”四面体字母。

Matsugi, Makoto: "An Efficient Sulfenylation of Aromatics Using Highly Active Quinone Mono O,S-Acetal Bearing a Pentafluorophenylthio Group"Tetrahedron Letter. 42. 1077-1080 (2001)

Matsugi, Makoto：“使用带有五氟苯硫基团的高活性醌单 O,S-缩醛进行芳香族化合物的有效磺酰化”四面体字母。

Kita, Yasuyuki: "Convenient Enzymatic Resolution of Alcohols Using Highly Reactive, Nonharmful Acyl Donars, 1-Etoxyvinyl Esters"Journal of Organic Chemistry. 65. 83-88 (2000)

Kita，Yasuyuki：“使用高反应性、无害的酰基供体、1-乙氧基乙烯基酯，方便地酶促拆分醇”有机化学杂志。