1999 Fiscal Year Final Research Report Summary
Chiral Processes towards Effective Synthesis of Optically Active Drugs
| Project/Area Number |
09557183
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
KUNIEDA Takehisa Kumamoto Univ., Fac. Pharm. Sci., Professor, 薬学部, 教授 (80012649)
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| Co-Investigator(Kenkyū-buntansha) |
OHZEKI Masakatsu Tanabe Seiyaku Co., Ltd., Institute of Pharmaceutical Research, Department Head, 医薬育成研究所, 部長研究員
MATSUNAGA Hirofumi Kumamoto Univ., Fac. Pharm. Sci., Research Associate, 薬学部, 助手 (10274713)
ISHIZUKA Tadao Kumamoto Univ., Fac. Pharm. Sci., Associate Professor, 薬学部, 助教授 (60176203)
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| Project Period (FY) |
1997 – 1999
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| Keywords | 2-Oxazolone / 2-Imidazolone / 2-Oxazolidinone / 2-Imidazolidinone / Chiral Auxiliaries / Chiral Ligands / Kinetic Resolution |
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| Research Abstract |
The aim of the study is to reveal the scope and limitations of the newly developed "roofed" heterocyclic auxiliaries with conformational rigidity and steric congestion as chiral sources for highly enantiocontrolled reactions.
1. Development of highly efficient chiral auxiliaries:
The optically active "roofed" 2-oxazolidinones and 2-imidazolidinones readily obtained from optical resolution with "MAC-acid" (2-exo-meloxy-1-apocamphanecarboxylic acid) or by kinetic resolution with oxazaborolidine catalysts have proved to serve as extremely powerful chiral auxiliaries in a variety of asymmetric reactions including the amidoalkylation and the Diels-Alder reaction.
2. Development of highly efficient chiral amino alcohols:
(a) chiral ligands: The chiral cis-2-aminoalcohols derived from ring-opening of the above tricyclic 2-oxazolidinones played a promising role in performing the high level of catalytic chiral discrimination (e.g. enantioselective borane reduction of ketones, asymmetrization of meso- 1,3-diacetyl-2-imidazolidinones).
(b) chiral reactants: The alkoxide of the sterically congested 2-aminoalcohols served well as chiral discriminating agents for highly efficient dissymmetrization of meso- 1,3-diacetyl-2-imidazolidinones and meso-dicarboxylic anhydrides.
(c)CィイD22ィエD2-symmetrical bis(oxazoline) ligands: The use of sterically congested CィイD22ィエD2-symmetrical bis(oxazoline) ligands derived from the above amino alcohols provided the unexpected enantioselection for aldol reactions catalyzed by the Cu(II) complexes, which was an important findings for a design of new chiral synthetic processes.
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