| Project/Area Number |
08672419
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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) |
OHBA Masashi Kanazawa University, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (60115219)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | alkaloid synthesis / asymmetric induction / beta-lactam / lycorane / 1beta-methylcarbapenem / 4-oxo-2-azetidineacetic acid / radical cyclization / thienamycin / テトラヒドロパルマチン / カルバペネム / PS-5 / チレニン / レンノキサミン |
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| Research Abstract |
Bu_3SnH-mediated regio- and stereoselective radical cyclizations of alpha-holo amides have been examined. The results are summarized below.
1. The 4-exo radical cyclization of N-vinylic alpha-halo amides, bearing a chiral auxiliary on the nitrogen atom or at the alpha-position of the carbonyl group, was found to proceed with high degree of diastereoselectivy to give optically active beta-lactams. The methods were applied to the synthesis of optically active carbapenem antibiotics such as (+) -PS-5, (+) -thienamycin and 1beta-methylcarbapenem.
2. The 5-endo radical cyclization of N- (1-cyclohexenen-1-yl) -alpha-haloacetamides bearing a chiral auxiliary on the nitrogen atom was found to proceed with moderate degree of diastereoselectivy t give optically active octahydroindol-2-ones. The method was applied to the total synthesis of (-) -gamma-lycorane.
3. The radical cyclization of N- (2-phenylthio-1-cyclohexenen-1-yl) -alpha-haloacetamies has been examined, and it was found that the course of the cyclizations was atrikingly affected by the reaction temperature employed. Thus, at room temperature, 4-exo cyclization predominated, and at higher temperature (in boiling toluene), 5-endo cyclization predominated.
4. The kN-vinyl-2-bromobenzamides or N-vinyl-2- (2-bromophenyl) acetamides bearing a phenylthio group at the terminus of their N-vinylic bond were found to undergo radical cyclization in a 5-exo-trig or in a 6-exo-trig manner effectively to give isoindolone and isoquinolinones, respectively. The methods were applied to the synthesis of some alkaloids such as chilenine, lennoxamine, tetrahydropalmatine and saulatine.
5. The N- [o- (2-propenyl) phenyl] -2,2-bis (phenylthio) acetamides were found to undergo radical cyclization in an 8-endo-trig manner to give benzoazocinone derivatives.
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