2013 Fiscal Year Final Research Report
Novel synthetic studies of heterocycles containing nitrogen by reductive ring expansion of oximes and their application to synthesis of candidate compounds for clinical studies.
| Project/Area Number |
23590001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
CHO HIDETSURA 東北大学, 薬学研究科(研究院), 客員教授 (40511910)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 水素化ジイソブチルアルミナム(DIBALH) / 水素化ジクロロアルミニウム(AlHCl2) / DIBALHによる還元的環拡大反応 / オキシムの転位反応 / ヒドロキシルアミン / AVP antagonist / 17 beta-HSD3 inhibitor / URAT-1 inhibitor |
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| Research Abstract |
The reductive rearrangement of various cyclic and acyclic oximes with aluminum reductants (DIBALH, AlHCl2 etc.) was performed to afford various secondary amines. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring.
The reaction proceeds through a three-centered transition state via a stepwise mechanism, because the potential energy curve along the intrinsic reaction coordinate had two maxima and the partial phenonium cation intermediate. The preference of the migration of a substituent was clarified that the more electron-rich group migrated preferentially to give the corresponding compounds. Their application to synthetic studies of several candidate compounds (AVP antagonist, 17 beta-HSD inhibitor, URAT-1 inhibitor) for clinical studies was demonstrated. Therefore, this reaction could be of practical use for the synthesis of fine chemistry and medicinal chemistry.
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