2001 Fiscal Year Final Research Report Summary
Combinatorial Synthesis of Peptide Mimetics Containing Unnatural Amino Acid Utilizing Homogeneous Catalyzed Reactions
| Project/Area Number |
11450344
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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 | 一般 |
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| Research Field |
Synthetic chemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
DOI Takayuki Graduate School of science and Engineering, Tokyo Institute of Technology, Associate Professor, 大学院・理工学研究科, 助教授 (90212076)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Takashi Graduate School of science and Engineering, Tokyo Institute of Technology, Professor, 大学院・理工学研究科, 教授 (80110724)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Homogeneous Catalyzed Reaction / Asymmetric Hydrogenation / Mizoroki-Heck Reaction / Carbonylation / Solid-phase Synthesis / Combinatorial Synthesis / Peptide Mimetics / Cyclic Peptides |
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| Research Abstract |
The secondary structures (β-sheet, β-turn, α-helix) of protein play an important role in their interactions with receptors and enzymes to control a multitude of biological processes. Many researchers have been engaged in the development of mimics of these secondary structure motifs for drug discovery efforts and in particular the utilization of combinatorial libraries of these "templates" to probe biological structure-activity relationship. Much attention has been directed toward solid-phase methods development for the synthesis of libraries for use in biological discovery efforts.
(i) Conformationally constrained 10-membered cyclic diamide was designed and synthesized. Sequential asymmetric hydrogenation of bis-cinnamic acid derivatives provided the core part of the HIV protease inhibitor in enantiomerically pure form.
(ii) Palladium-catalyzed Mizoroki-Heck reaction of solid-supported dehydroalanine with various aryl iodides, followed by rhodium-catalyzed asymmetric hydrogenation afforded a library of peptides containing unnatural amino acids.
(iii) Palladium-catalyzed carbonylation-cyclization of peptides including iodobenzyl amine derivatives furnished a library of cyclic peptides containing a benzene ring connecting at the ortho, metha, and para-positions.
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