2000 Fiscal Year Final Research Report Summary
Simulation and Structural Factor of the Coenzyme Model for C_1-unit Transfer
| Project/Area Number |
09640649
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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 |
Organic chemistry
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| Research Institution | Waseda University |
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Principal Investigator |
TADA Masaru Waseda University, School of Science and Engineering, Professor, 理工学部, 教授 (90063651)
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| Project Period (FY) |
1997 – 2000
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| Keywords | Methanogens / Coenzyme Model / F_<430> Model / methyl transfer / thiyl radical / hyper valency |
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| Research Abstract |
This year we studied mainly the synthesis of metanopterin model and model reactions of coenzyme M.We have been investigating the new route to synthesize pteridines starting from 2,3-dicyanopyrazine and we extended the route for the syntheses of pteridines as metanopterin model. The important step of this route is the derivation of an amine by the substitution of one of the cyano group with amine group. Ammonia as a nucleophile, however, resulted in complex product mixture. Therefore, we carried out the substitution by allyl amine or propargyl aimine to get the mono-amino derivative and removed the allyl or propargyl group by Pd(0) complex or other reduction reagents. The synthesis of pteridine models has almost finished at the present srtage. We have studied another route of pteridine syntheses starting from pyrimidine derivatives and a rout starting form 6-aminouracil is nearly ended.
Another theme of this study is a model reaction of methyl transfer by coenzyme M and we clarified the important role of thiyl radical. The transfer is essentially an S_H2 substitution between methyl radical and thiyl radical. At the transition state, sulfur is coordinated by another ligand forming a (10-S-3) hypervalent state. We proposed the stabilization of the transition state by this hypervalent state from experimental findings. From these considerations, we proposed the importance of the hypervalency of thiyl radical in the DNA synthesis, which is catalyzed by ribonucleotide reductase and the reaction is triggered by the hydrogen transfer from ribose to thiyl radical, a thermodynamically unfavorableprocess. We have obtained preliminary results supporting this proposal. There are number of enzymatic reactions involving the thiyl group of cystein residue. Hypervalency may be a possible pattern of thiyl group participation in enzyme systems in many cases though not all. The experimental findings and the concept described above may be valuable in understanding enzymatic reactions.
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