1986 Fiscal Year Final Research Report Summary
One Step Synthesis of 1,4-Benzodiazepines
| Project/Area Number |
60570973
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
MORI Miwako Faculty of Pharmaceutical Sciences, Hokkaido University, Instructor, 薬学部, 助手 (80001981)
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| Project Period (FY) |
1985 – 1986
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| Keywords | Palladium catalyzed carbonylation / <Pd(PPh_3)_4> / carbonylation / benzodiazepine / quinazoline / antibiotics / tomaymycin / ネオスラマイシン |
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| Research Abstract |
We have already shown the synthetic procedure of 1,4-benzodiazepines from o-halo-anilines and amino acid derivatives by use of palladium catalyzed carbonylation. Using this method, the total syntheses of pyrrolo-1,4-benzodiazepine antibiotics, namely, tomaymycin, prothracarcin, and SEN-215 were achieved from o-haloaniline derivatives and hydroxy-l-proline as the optically active forms. The structures of prothracarcin and SEN-215 were determined synthetically as E-form, respectively. Moreover, a carbon framwork of neothramycin was constructed from o-iodoaniline and l-proline by four steps including palladium catalyzed carbonylation and anodic oxidation of carbon <alpha> to nitrogen. The total synthesis of neothramycin was effected from the same intermediate for the synthesis of tomaymycin and SEN-215. During the course of this study, it was found that the quinazoline skeleton was easily formed from o-iodoaniline and five membered lactams. By the application of this method, new synthetic method of quinazoline was developed and vasicinone and rutecarpine were synthesized.
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