| Project/Area Number |
11672099
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
ISHIBASHI Hiroyuki Kanazawa University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70028869)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Yoshifumi Kanazawa University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (70311678)
TAMURA Osamu Kanazawa University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30257141)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | radical cyclization / vinyl sulfide / mappicine ketone / manganese (III) acetate / regiochemistry / physostigmine / neophyl rearrangement / oxidative radical cyclization / エリスリナン / エナミド / イパルビジン / パンクラシン / アファノルフィン |
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| Research Abstract |
1. Radical cyclization of ω-haloalkenes having a sulfur atom or a nitrile group at the terminus of their alkenic bond was found to undergo in an exo manner exclusively. A mechanistic rationalization for the results was proposed and the methods were applied to the syntheses of the key intermediates for (±)-ipalbidine and (±)-physostigmine.
2. Stereoselective synthesis of (3R^*, 3aS^*, 7aS^*)-3-aryloctahydroindol-2-ones using 5-exo radical cyclization was developed and the method was applied to a formal synthesis of (±)-pancracine.
3. Formation of 6-endo cyclization products by radical reaction of N-vinylic 2-iodobenzamides was found to proceed through a consecutive 5-exo aryl radical cyclization and neophyl rearrangement.
4. In the course of the study on the radical cyclization of N-(ο-bromobenzyl) enamides, we found a first example of the formation of 6-endo cyclization product onto alkene having no substituent on the alkenic bond. We also found that the enamides having two phenylthio groups at the terminus or the N-vinylic bond underwent radical cyclization in a 5-exo manner exclusively. The latter method was applied to the synthesis of a model compound of mappicine ketone, an anti-herpesvirus compound.
5. The use of an iodine atom is recognized to give a better result than does that of a chlorine atom in the radical reactions of halogeno compounds. We found, surprisingly, that in the 5-endo cyclization of α-halo amides, the use of a chlorine atom gave the cyclization products in high yields, whereas that of an iodine atom gave only a limited amount of the expected cyclization product.
6. Mu(OAc)_3/Cu(OAc)_2-mediated oxidative radical cyclization of α-(methylthio) amides was developed and the method was applied to a concise construction of an erythrinane skeleton.
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