| Project/Area Number |
17590016
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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 | Toho University |
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Principal Investigator |
YOKOYAMA Yuusaku Toho University, Faculty of Pharmaceutical Sciences, Associate Professor (10095325)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Amino Acid / Decarboxylation / Bromination / Protecting Group / IDO Inhibitor / Tryptophan / Water / Organic Synthesis / 生体分子 / エフェドリン / アミノアルコール / ベンズアルデヒド / 無保護アミノ酸 / 位置選択的 / IDO阻害活性 / 芳香族アミノ酸 / 水溶液 |
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| Research Abstract |
1. We succeeded that the bromination of unprotected aromatic amino adds such as phenylalanine, tyrosine, and phenylglycine using bromoisocyanuric acid sodium salt as a brominating reagent under strong acidic condition (60-90% aqueous solution of H_2SO_4) gave the brominated products in good yields. It is very interesting that protection of amino group was not required in the presence of B r_+ that was possessed oxidizing property.
2. We synthesized the most active inhibitor of indole 2.3-dicorygenase (IDO) by applying the one-step synthetic method of N-acetyltryptophan from indole and serine that was developed by us. Since IDO inhibitors have a big potential as an anti-cancer or anti-Alzheimer disease drug having a new mode of mechanism, we applied this compound to patent last year.
3. In 1942, Akabori reported that the reaction of N-methylalanine with benzaldehyde gave the mixture of diastereoisomer of ephedrine in low yield. By our reinvestigation of this reaction, we found the serious amount of oxazolidine derivative as a by-product that was formed by the reaction of another benzaldehyde with resulted ephedrine. The yield of ephedrine was greatly improved to by heating the reaction mixture with 5% AcOH. The reaction of benzaldehyde having electron donating group on benzene ring gave the aminoalcohol derivatives in excellent yield (up to 87%) . This reaction is not only a new type of the reaction of amino acid that is involved a decarboxylative C-C bond forming reaction on the asymmetric carbon atom but also useful one-pot synthetic reaction aminoalcohol that was involved various important drugs as fundamental skeleton..
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