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.

在这个科学项目中，不对称合成具有抑制细胞粘附活性和抗肿瘤活性的生物活性化合物是基于酶的功能进行的。利用酶促作用合成了具有细胞粘附抑制活性的巨球内酯A。关键手性中间体甲基(4R,5S)-5-乙酰氧基-4-苄氧基-(2E)-己烯酸酯通过脂肪酶对映选择性水解得到。以4-碘吲哚和(2R,3S)-环氧丁酸甲酯为原料，合成了具有抗菌活性的(-)-创新霉素。该手性中间体也是利用脂肪酶对外消旋(2,3)-反式-2-乙酰氧基-3-氯丁酸酯进行对映选择性水解得到的。利用酶促作用合成了具有十氢化-5,5,8a-三甲基萘骨架的十氢化萘型手性合成物。由此得到的手性合成子转化为具有强烈琥珀型香气的(-)-ambrox和海洋天然产物(+)-zonarol。根据酶的功能，还实现了肽基核苷类抗生素、尼克霉素B和维生素E的不对称合成。

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。

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

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。