Development of Efficient Chiral Synthetic Process of Bioactive Compounds.

生物活性化合物的高效手性合成工艺的开发。

• 批准号: 07557305
• 负责人: KUNIEDA Takehisa
• 金额: $ 1.22万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557305/
• 关键词: 2-Amino alcohol; 2-Oxazolone; 2-Oxazolidinone; Asymmetric synthesis; Chiral auxiliary; 2-Imidazolone; 2-Imidazolidinone; Chiral synthesis; aldol反応

1.Development of Diastereoselective Procedures.(1) Both enantiomers of sterically congested 2-oxazolidinones and 2-imidazolidinones, which served as efficient chiral auxiliaries, were synthesized by [4+2] cycloaddition of cyclic dienes with 2-oxazolone and 2-imidazolone. The utilities of these auxiliaries in asymmetric synthetic reactions such as alkylations, the Diels-Alder reactions, Michael reactions and aldol reactions were revealed.(2) The 2-oxazolidinones were hydrolyzed to conformationally fixed 2-amino alcohols of synthetic significance. The lithium salts of N-sulfonyl derivative of amino alcohols thus obtained cleaved meso-dicarboxylic anhydrides to the half esters with almost perfect diastereoselectivity. In contrast, zinc salts reacted with the anhydrides with opposite selectivity.2.Development of Enantioselective Procedures.N,N-Dialkylamino alcohols and N-sulfonylamino alcohols which were derived from ringcleavage of the 2-oxazolidinones served as equally effective catalysts in ethylation of aldehydes with ZnEt_2, but interestingly showed completely reversed enantioselectivity.

1.非对映选择性程序的发展。(1)采用环二烯与2-恶唑酮和2-咪唑酮[4+2]环加成的方法合成了立体拥塞的2-恶唑烷酮和2-咪唑烷酮对映体，作为高效的手性助剂。揭示了这些助剂在烷基化反应、Diels-Alder反应、Michael反应和醛醇反应等不对称合成反应中的应用。(2)将2-恶唑烷酮水解成具有合成意义的构象固定的2-氨基醇。氨基醇的n -磺酰基衍生物的锂盐因此得到了具有几乎完全非对映选择性的裂解中二羧酸酐半酯。相反，锌盐与酸酐反应具有相反的选择性。对映体选择程序的发展。由2-恶唑烷酮环裂解得到的N，N-二烷基氨基醇和N-磺酰氨基醇在ZnEt_2催化醛的乙化反应中同样有效，但有趣的是，它们表现出完全相反的对映选择性。

项目成果

Tadao Ishizuka: "2-Oxazolone as Versatile Building Block for Stereodefined Construction of 2-Amino Alcohols." Yakugaku Zasshi. 115. 460-475 (1995)

Tadao Ishizuka：“2-恶唑酮作为 2-氨基醇立体结构的通用结构单元。”

Hirohumi Matsunaga: "Chiral Electrophilic "Glycinal" Equivalents. New Synthons for Optically Active alpha-Amino Acids and 4-substituted 2-Oxazolidinones." Tetrahedron. 53. 1275-1294 (1997)

Hirohumi Matsunaga：“手性亲电“甘氨酸”等价物。光学活性 α-氨基酸和 4-取代 2-恶唑烷酮的新合成子。”

Kouyama Takahumi: "Facile Synthesis of (+)- and (-)-Geissman-Waiss Lactones" Heterocycles.44. 479-486 (1997)

Kouyama Takahumi：“( )- 和 (-)-Geissman-Waiss 内酯的简易合成”杂环。44。

Tadao Ishizuka: "2-Oxazolone asBuilding Block for Chiral Auxiliaries -- Extremely Powerful Chiral 2-Oxazolidinone and 2-Aminoalcohol Auxiliaries --" Advances in Pharmaceutical Sciences. 12. 23 (1996)

Tadao Ishizuka：“2-恶唑酮作为手性助剂的构建模块——极其强大的手性 2-恶唑烷酮和 2-氨基醇助剂——”制药科学进展。

Hideo Imado: "Highly Effective Diastereodifferentiation of meso-Dicarboxylic Anhydrides Using Sterically Congested Chiral N-Sulfonylaminoalcohols" Tetrahedron Lett.36. 931-934 (1995)

Hideo Imado：“使用空间拥挤的手性 N-磺酰氨基醇对内消旋二羧酸酐进行高效非对映分化”四面体 Lett.36。