Development of Antitumor Compounds Using the Chiral Benzaldehyde
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Kanazawa University|
HANAOKA Miyoji Faculty of Pharmaceutical Sciences, Kanazawa University Professor, 薬学部, 教授 (80028844)
KATAOKA Osamu Faculty of Pharmaceutical Sciences, Kanazawa University Research Associate, 薬学部, 助手 (40303292)
MUKAI Chisato Graduate School of Natural Science and Technology, Kanazawa University Professor, 大学院・自然科学研究科, 教授 (70143914)
杉本 雄一 金沢大学, 薬学部, 助手 (90226465)
|Project Period (FY)
1997 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥10,800,000 (Direct Cost : ¥10,800,000)
Fiscal Year 1999 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1998 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1997 : ¥6,700,000 (Direct Cost : ¥6,700,000)
|Keywords||chiral benzaldehyde / styryllactone / chiral aldol reaction / stereoselective reaction / chiral synthesis / lactone structure / antitumor compound / 不斉ベンズアルデヒド / ゴニオヘプトライド / 1,3-双極子環状付加反応 / ニッコマイシン / ゴニオフピロン / チオエステル / タキソ-ル / 立体選択反応|
1. Chirai aldol reaction of the chiral benzaldehyde with silyl ketene acetals afforded anti-aldol products with highly stereoselectivity. Thus, chirality of the chiral benzaldehyde was effectively transformed to a chiral carbon chain.
2. Aldol reaction of the chiral benzaldehyde with a titanium enolate derived form a thioester gave stereoselectively an anti-aldol product.
3. Common synthetic intermediate having four continuous asymmetric carbons was synthesized in highly stereoselective manner and highly optical yield from the chiral benzaldehyde through twice aldol reactions. Total synthesis of styryllactones having a 5-membered lactone, goniofufurone, goniobutenolide A and B was achieved.
4. Conversion of a 5-membered lactone to a 6-membered lactone through a lactol was developed. According to this method, styryllactones having a 6-membered lactone, goniodiol, goniotriol, 8-acetylgoniotriol, altholactone, and 9-deoxygoniopypyrone were synthesized.
5. Chiral total synthesis of goniofupyrone was succeeded. This synthesis established the structure of goniofupyrone including absolute stereochemistry and revised the previously proposed structure.
6. The structure of gonioheptolide A was revised by its synthesis from goniofupyrone. The proposed 8-membered lactone structure was found to be incorrect.
7. Amino acid part of AI-77B, an antiulcerogenic antibiotic, and AI-77B analogue were synthesized from the chiral benzaldehyde.
8. 1,3-Dipolar cycloaddition of chiral nitrons, derived form the chiral benzaldehyde, with olefins gave stereoselectively cis-3,5-disubstituted isoxazolidines.
Research Output (9results)