1999 Fiscal Year Final Research Report Summary
Synthesis of Silicon-containing Terahydroisoquinolines for Exploring Novel Biological Activity
| Project/Area Number |
09672166
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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 | Science University of Tokyo |
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Principal Investigator |
HOSHINO Osamu Science University of Tokyo, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40084420)
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| Project Period (FY) |
1999
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| Keywords | silylation / silylmethylation / N-pivaloyltetrahydroisoquinoline / t-BuLi-TMEDA / intramolecular rearrangement / N-pivaloyltetrahydroisoquinolin-7-ol / N-formamidyl group / N-trifluoroacetyltetrahydroisoquinoline |
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| Research Abstract |
1. Silylation and silylmethylation of N-pivaloyl-7-benzyloxy-6-methoxytetrahydroisoquinoline in the presence of t-BuLi-TMEDA in THF at -78℃ gave the conresponding 1-trimethylsilyl- and 1-trimethyl-silylmethyl-tetrahydroisoquinolines in fair yield. Their debenzylation with catalytic hydrogenation afforded 1-trimethylsilyl- and 1 -trimethylsilylmethyl-N-pivaloyltetrahydroisoquinolin-7-ols in good yield.
2. Silylation of N-trifluoroacetyl congener under the similar conditions gave N-pivaloyl product, which was formed by replacement of N-trifluoroacetyl group with t-butyl anion.
3. Unexpectedly, lead tetraacetae oxidation of l-trimethylsilyl- and 1-trimethylsilylmethyl-N-pivaloyltetrahydroisoquinolin-7-ols was unfruitful. For purpose of preparing N-trifluoroacetyl compounds in place of N-pivaloyl ones, similar reaction of N-formamidyl cogener was performed. However, satisfactory results were not obtained. Furthermore, examination on N-formamidino cogener should be required.
4. In order to examine Bischler-Napieralski reaction of N-(2-phenethyl)trimethylsilylpropionamide, trimethylsilylmethylation of N-(2-phenethyl)acetamide under basic conditions was carried out to give N-(2-phenethyl)trimethylsilylacetamide exclusively. It was assumed that C-silylation by intramolecular rearrangement of N-silyl group occured.
5. Biological evaluation on synthesized compounds is in progress.
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