Asymmetric syntheses of bioactive compounds possessing inhibition activity of cell adhesion and antitumour activity

具有细胞粘附抑制活性和抗肿瘤活性的生物活性化合物的不对称合成

• 批准号: 10672002
• 负责人: AKITA Hiroyuki
• 金额: $ 1.66万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672002/
• 关键词: Macrosphelide A; Chuangxinmycin; (-)-Ambrox; (+)-Zonarol; Nikkomycin B; Vitamin E; lipase; Total synthesis; 抗生物質; chuangxinmycin; Nikkoroycin B

In this scientific program, asymmetric syntheses of bioactive compounds possessing inhbition activity of cell-adhesion and antitumour activity were carried out based on enzymatic function.1. Total synthesis of macrosphelide A possessing inhibition activity of cell-adhesion was achieved based on enzymatic function. The key chiral intermediate, methyl (4R,5S)-5-acetoxy-4-benzyloxy-(2E)-hexenoate was obtained by the enantioselective hydrolysis using lipase of the corresponding racemate.2. Total synthesis of (-)-chuangxinmycin having antimicrobial activity was achieved based on the reaction of 4-iodoindole and methyl (2R,3S)-epoxy butanoate. This chiral intermediate was also obtained based on the enantioselective hydrolysis using lipase of the racemic (2,3)-trans-2-acetoxy-3-chloro butanoate.3. The synthesis of decalin type chiral synthon possessing decahydro-5,5,8a-trimethyl-naphthalene skeleton was achieved based on enzymatic function. Thus obtained chiral synthons were converted into (-)-ambrox bearing a powerful amber-type aroma and marine natural product, (+)-zonarol.4. Asymmetric syntheses of peptidyl nucleoside antibiotic, nikkomycin B and vitamin E were also achieved based on enzymatic function.

在这个科学计划中，基于酶促功能进行了具有诱导细胞粘附和抗肿瘤活性的生物活性化合物的不对称合成。1。基于酶促功能，实现了巨磷酸A具有抑制活性的总合成。关键的手性中间体，甲基（4R，5s）-5-乙氧基-4-苯甲酰氧基 - （2E） - 己酸酯是通过使用相应种族酸盐的脂肪酶的对映选择性水解获得的。2。 （ - ） - 具有抗菌活性的（ - ） - 基于4-碘吲哚和甲基（2R，3S） - 环氧丁烷酸盐的反应，达到了抗菌活性的总合成。还基于对映选择性水解的脂肪酶（2,3） - Trans-2-Acetoxy-3-氯丁酸丁酸丁酸酯3。具有decahydro-5,5,8a-三甲基萘骨架的脱甲素型手性合成的合成是基于酶促功能实现的。因此，获得的手性合成子被转换为（ - ） - 带有强大的琥珀色香气和海洋天然产物，（+） - Zonarol.4。肽基核苷抗生素，Nikkyomycin B和维生素E的不对称合成也是基于酶促功能来实现的。

项目成果

H. Akita, Cheng Yu Chen and S. Nagumo: "A Highly Stereoselective Synthesis of the Versatile Chiral Synthons Possessing Two Stereogenic Centers. The Formal Total Syntheses of (-)-Oudemansins A, B and X."Tetrahedron : Asymmetry. 5. 1207-1210 (1994)

H. Akita、Cheng Yu Chen 和 S. Nagumo：“具有两个立体中心的多功能手性合成子的高度立体选择性合成。(-)-Oudemansins A、B 和 X 的正式全合成。”四面体：不对称性。

M. Ono, C. Saotome, and H. Akita: "The Reaction of 4,5 Epoxy-2(E)-Hexenoate and Secondary Amines, Total Synthesis of (-)-Osmundalactone and (-)-Forosamine."Heterocycles. 51. 1503-1508 (1999)

M. Ono、C. Saotome 和 H. Akita：“4,5 环氧-2(E)-己烯酸酯和仲胺的反应，(-)-紫萁内酯和 (-)-Forosamine 的全合成”。杂环。

H. Akita, I, Umezawa, M. Nozawa and S.Nagumo: "Total Synthesis of (-)-Oudemansin X Based on Enzymatic Resolution Using Immobilized Lipase."Tetrahedron : Asymmetry. 4. 757-760 (1993)

H. Akita、I、Umezawa、M. Nozawa 和 S.Nagumo：“基于使用固定化脂肪酶的酶促拆分的 (-)-Oudemansin X 的全合成”。四面体：不对称性。

H. Akita, C-Y. Chen and K. Uchida: "A Formal Total Synthesis of Nikkomycin B Based on Enzymatic Resolution of a Primary Alcohol Possessing Two Stereogenic Centers."Teterahedron : Asymmetry. 6. 2131-2134 (1995)

H.秋田，C-Y。

M. Ono, C. Saotome, and H. Akita: "Total Syntheses of N-Trifluoroacetyl-L-daunosamine, N-Trifluoroacetyl-L-acosamine, N-Benzoyl-D-acosamine, and N-Benzoyl-D-ristosamine from An Achiral Precursor, Methyl Sorbate."Heterocycles. 45. 1257-1261 (1997)

M. Ono、C. Saotome 和 H. Akita：“N-三氟乙酰基-L-道诺胺、N-三氟乙酰基-L-阿糖胺、N-苯甲酰基-D-阿糖胺和 N-苯甲酰基-D-瑞斯托胺的全合成