Catalytic enantioselective diels-alder reaction of furan and synthetic studies on antitumor agent ottelione A = 촉매를 이용한 퓨란의 입체 선택적인 diels-alder 반응 연구와 천연물 ottelione A의 합성법에 관한 연구

다국어 초록 (Multilingual Abstract)

I. Catalytic enantioselective Diels-Alder reaction of furan

Diels-Alder reaction is one of the most powerful synthetic methodologies for the construction of cyclic ring. Chiral oxazaborolidinium salts have been shown to be remarkably effective catalysts for broad range of enantioselective Diels-Alder reaction. The absolute stereochemical course of each of these reactions can be predicted by a logical and clear mechanistic reasonable. The face selectivity of the enantioselective Diels-Alder reaction depends on the structural type of the dienophile component.
The catalytic Diels-Alder reaction was applied to several dienophiles, in the presence of furan, the reaction proceeds at low temperature and gives high enantioselectivity.


II. Synthetic studies on antitumor agent ottelione A and anticancer activities of their derivatives

A screening and synthesis aimed at the discovery of new anticancer drug have done for natural compounds extracted from the korean plant Ottelia alismoides. We report their isolation, synthesis, structural determination and biological activity, showing components with the potent therapeutic values. These natural products and synthetic compounds show remarkable in vitro cytotoxicity against cancer cell line.
Two diastereomeric Otteliones, ottelione A and B have been isolated from the plant Ottelia alismoides from Korea and accumulated for biological mechanistic study explaining their anticancer activity. In addition, we found new fractions which show cytotoxicity against cancer cell line and have not been known previously, indicating the discovery of new anticancer compounds.
The stereoselective synthetic studies on ottelione A are performed starting from the Diels-Alder adduct of cyclopentadiene and iodoquinone monoketal. The requisite chiral centers are controlled by catalytic enantioselective Diels-Alder reaction as one step. The chiral Diels-Alder adduct was obtained in >98% yield and 97% enantiomeric excess. Subsequent Luche reduction, ozonolysis, Wittig reaction and oxidation provided a key lactone intermediate in good yield. Many various ottelione derivatives, which are valuable to investigate SAR (structure Activity Relationship) of otteliones are synthesized by several transformation methods from the lactone intermediate.

목차 (Table of Contents)

• Part I . 입체 선택적인 Diels-Alder 반응연구
• Ⅰ. 서론 --------------------------------------------- 1
• Ⅱ. 본론 --------------------------------------------- 6
• Ⅲ. 결론 --------------------------------------------- 11
• Ⅳ. 실험 방법 ---------------------------------------- 12
• Part II . 천연물 Ottelione 의 합성법 연구
• Ⅰ. 서론 --------------------------------------------- 18
• Ⅱ. 본론 --------------------------------------------- 21
• 1. Ottelione A 의 입체 선택적인 합성법 및 그 유도체들의 합성
• 2. 합성한 ottelione 유도체들의 항암효과 측정 및 SAR 분석
• Ⅲ. 결론 --------------------------------------------- 38
• Ⅳ. 실험 방법 ---------------------------------------- 39
• Ⅴ 참고 문헌 ----------------------------------------- 49