1992 Fiscal Year Final Research Report Summary
Synthesis of Monofluoro Building Blocks Designed from Fine Chemistry Viewpoint and Development of Fluorine-containing Medicinals
| Project/Area Number |
02557086
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Toyama Medical & Pharmaceutical University |
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Principal Investigator |
TAKEUCHI Yoshio Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (20111750)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Tamiko Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences Re, 薬学部, 助手 (10115181)
ARAI Yoshitsugu Toyama Medical & Pharmaceutical University Faculty of Pharmaceutical Sciences re, 薬学部, 助手 (10115157)
KOIZUMI Toru Toyama Medical & Pharmaceutical Scieces Professor, 薬学部, 教授 (40012611)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Monofluoro Building Blocks / Multifunctional Carbon Compounds / Tertiary Alkyl Fluorides / alpha-Fluoro-alpha-amino Acid / Fluorinated Tropanes / Fluorine-containing Medicinals / NMAD Receptor / Molecular Design |
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| Research Abstract |
1) Among the various monofluoro building blocks designed, 1-6, synthesis of the four compounds 1-4 was achieved. However, the isolation of the selenenyl derivative 5 and the fluoroethene equivalent 6 was unsuccessful due to the instability caused by the multifunctional carbon structures.
2) Synthesis of the chiral tropane precursors, 7 and 8, was achieved. However. further efforts to convert them into chiral tropanes was abandoned because this pathway involves some reactions with unsatisfactory yields.
3) As to the development of the general entry to the novel tertiary alkyl fluorides, we succeeded to get to the target structure 13 by two routes, i. e., the alkylation of 11 obtained from 9 via 10 and the alkylation of 12 obtained from 9.
4) The synthesis of various precursors for alpha-fluoro-alpha-amino acids, including 15 and 16, has been achieved. However, the target compounds could not be isolated due to the rather drastic reaction conditions employed for the final stage and also to the instability of the target compounds.
5) Four compounds 14-17 were tested for fencyclidine inhibitory activity and monofluorotropane 18 was tested for nicotinic activity. However, all of them were found to be not so effective as we had expected.
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