臺灣博碩士論文加值系統

中文摘要:
在研究抗癌藥物的合成過程中，我們實驗室發現以氫還原MOM保護的比咯苯偶駢(PBD)內醯胺會進行特別之胺鍵斷裂，我們推測它們是以3-aza Grob斷裂來進行開環反應，最近研究具有醚類 (如: MOM, MEM, SEM, BOM, MTM)保護之芳香族內醯胺，氫還原他們亦會進行相同之斷裂開環反應，因此，我們相信這是一新型之斷裂反應；為了進一步證明此一反應機構，我們設計合成以THT、THF保護的芳香族內醯胺做實驗，結果氫還原它們進行相同之3-aza Grob斷裂開環反應，這印證我們的理論，因為在這種情形下，三個斷裂片段會殘留在同一分子上，經由穩定同位素實驗亦證實了我們的發現。
此外，我們也使用不同性質之還原試劑，如：Borane 類的還原試劑來作研究，實驗結果證實得到不相同之產物，我們亦擴展使用其他親核性試劑，如格里鈉試劑等做實驗，這些實驗正在研究中。

Abstract:
Heterolytic fragmentation is widespread and serves a useful reaction in organic synthesis. We have previously reported that an unusual heterocyclic fragmentation reaction occurs in hydride reduction of N-methoxymethylpyrrolo[2,1-c][1,4]benzo-diazepine-5,11-diones, the synthetic intermediates of a family of anticancer DNA alkylating agents known as pyrrolo[2,1-c][1,4]benzodiazepines. We postulated that this reaction proceeds via 3-aza-Grob fragmentation. We recently extended our studies to ether-protected aromatic lactams with 5- and 6-member rings. The results showed that hydride reduction of MOM, MEM, SEM and BOM-protected oxindole analogs gave ring-opening products via the same path as 7-membered ring lactams, N-methoxymethylpyrrolo [2,1-c][1,4]benzodiazepine-5,11-diones, in excellent yields.
In this report, we examined 3-aza-Grob fragmentation of hydride reduction of THF protected 3,4-dihydro-2（1H）-quinolinone analogs, THT and THF. The results demonstrate that various hydride reagents can reduce aromatic lactams via 3-aza-Grob fragmentation. Further examination by stable isotope studies supports our observations.

目 錄
目錄………………………………………………….Ⅰ
圖表目錄…………………………………………….Ⅱ
中文摘要…………………………………………….Ⅳ
英文摘要…………………………………………….Ⅴ
縮寫………………………………………………….Ⅵ
一、前言……………………………………………. P.1
二、研究動機………………………………………. P.6
三、結果與討論…….……………………………… P.12
四、結論………………………………….………… P.20
五、實驗部份……………………………………….P.23
六、參考文獻……………………………………….P.46

參考文獻
1. Petrusek, R. L.; Anderson. G. L.; Garner, T. F.; Fannin, Q. L.; Kaplan, D. J.; Zimmer, S. G.; Hurley, L. H. Biochemistry 1981, 20, 1111.
2. Arora, S. K. Acta Crystallogr. 1979, B35, 2945.
3. Hurley, L. H.; Boyd, F. L. TIPS 1988, 9, 402.
4. Hurley, L. H. J. Med. Chem. 1989, 32, 2027.
5. Suggs, J.W.; Wang, Y. S.; Lee, K. S. Tetrehedron Lett. 1985, 26, 4871.
6. Kameda, Y.; Leimgruber, W.; Batcho, A. D.; Schenker, F. J. Am. Cem. Soc., 1965, 87, 5793.
7. Weyersthal, P; Marschall, H. Fragmentation Reactions, in Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I. Eds; Pergamn Press, 1991, Vol. 6, p. 1044.
8. aThurston D. E.; Bose D. S. Chemical Reviews, 1994, 94, 433-465. b莊宏偉，高雄醫學院天然藥物研究所民國86年6月碩士論文。
9. Grob, C. A.; Schiess, P. W. Angew. Chem. Int. Ed. Engl. 1967, 6, 1.
10. Grob, C. A. Angew. Chem. Int. Ed. Engl. 1969, 8, 535.
11. Becker, K. B.; Grob, C. A. The Chemistry of Double-bonded Functional Groups. Patai, S., ed.; Wiley: N. Y., 1977, Part 2, p. 653.
12. Wang, J. J.; Hu, W. P.; Chung, H. W.; Wang, L. F.; Hsu, M. H. Tetrahedron 1998, 54, 13149-13154.
13. Wharton, P. S. J. Org. Chem. 1961, 26, 4781.
14. Wharton, P. S.; Hiegel, G. A.; Coombs, R. V. J. Org. Chem. 1963, 28, 3217.
15. Wharton, P. S.; Hiegel, G. A. J. Org. Chem. 1965, 30, 3254.
16. Caine, D. Org. Prep. Proced. Int. 1988, 20, 1.
17. Wang, J. J.; Hu, W. P. J. Org. Chem. 1999, 64, 5725.
18. Kruse, C. G.; Broekhof, N. L. J. M.; van der Gen, A. Tetrahedron Lett. 1976, 17, 1725.
19. Kruse, C. G.; Poels, E. K.; Jonkers, F. L.; van der Gen, A. J. Org. Chem. 1978, 43, 3548.
20. Thurston, D. E.; Kaumaya, P. T. P.; Hurley, L. H. Tetrahedron Lett. 1984, 25, 2649 and references cited therein.
21. Thurston, D. E.; Bose, D. S. Chem. Rev. 1994, 94, 433.
22. Greene, T.W.; Wuts, P. G. M. Protecting Groups in Organic Synthesis, 2nd ed.; John Wiley &Sons: New York, 1991.
23. Connor, D. S.; Klein, G. W.; Taylor, G. N.; Boeckman, R. K., Jr.; Medwid, J. B. Organic Synthesis;Wiley: New York, 1986; Collect. Vol. 6, p 101.
24. Hu, W. P.; Wang, J. J.; Tsai, P.C. J. Org. Chem. 2000, 65,xxxx.