| Project/Area Number |
09672166
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | Science University of Tokyo |
|---|
Principal Investigator |
HOSHINO Osamu Science University of Tokyo, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40084420)
|
|---|
| Project Period (FY) |
1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | silylation / silylmethylation / N-pivaloyltetrahydroisoquinoline / t-BuLi-TMEDA / intramolecular rearrangement / N-pivaloyltetrahydroisoquinolin-7-ol / N-formamidyl group / N-trifluoroacetyltetrahydroisoquinoline / N-ビバロイル基 / N-ホルムアミジノ基 / トブチルリチウム-TEMEDA / シリル化 / N-ビバロイル-7-テトラヒドロイソキノリノール / N-トリフルオロアセチル基 / 四酢酸鉛酸化反応 / 1位ケイ素置換7-テトラヒドロイソキノリノール / リチウムジイソプロピルアミド / シュロサ-塩基 / トリメチルシリル化 / トリメチルシリルメチル化 / N-トリメチルシリルアセチルアミド / 1-シリル-N-アシルテトラヒドロイソキノリン / 1-シリルメチル-N-アシルテトラヒドロイソキノリン |
|---|
| 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.
|
