1999 Fiscal Year Final Research Report Summary
Total synthesis of Macrocyclic Thiopeptide Antibiotic Constructing Ployheterocyclic Compounds and Unusual Amino Acids
| Project/Area Number |
10640532
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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 | Kanagawa University |
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Principal Investigator |
SHIN Chung-gi Applied Cheistry, Professor, 工学部・応用化学科, 教授 (20078306)
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| Co-Investigator(Kenkyū-buntansha) |
YONEZAWA Yasuchika Applied Cheistry, Assistant, 工学部・応用化学科, 助手 (70078335)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Thiostrepton antibiotics / Dehydropeptide / Dehydrothiazoleamino acid / Dehydrooxazoleamino acid / Polysubstituated pyridine / Micrococcin P, PィイD21ィエD2 / Cyclothiazomycin / Berninamycin |
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| Research Abstract |
The total syntheses of macrocyclic antibiotics, micrococcins P and PィイD21ィエD2 (1,2), were first achieved. These antibiotics have unique structures and are constructed of four components called Fragments A, B, C, and D. In particular, the structures of the central pyridine skeleton(Fragment A) and the exocyclic side-chain(Fragment D) of 1 and 2 are slightly different each other. First of all, after constructing the central 2, 3, 6-tristhiazolylsubstituted pyridine skeleton(Fragment A-C segment) (4) from ethyl 2-(2-bromoacetyl-6-dimethoxymethyl-3-pyridyl)-thiazole-4-carboxylate (3) in 11 steps, successive fragment condensations of 4 with ethyl 2-(Z)-1(O-t-butyldiphenylsilyl-L-threoylamino)-1-propenylthiazole-4-carboxylate and (S)-1-(O-methoxymethyl-L-threoylamino)-2-(O-methoxymethyl)-2-propanol (5) (the protected Fragment B and C moieties, respectively) gave the protected Fragment A-B-C-D segment 6. Subsequent deprotecting of all the protecting groups of 6 with trifluoroacetic acid and then cyclization by using BOP as condensing agent under high dilution gave the expected micrococcin P (1).
Furthermore, by various chemical modifications of the synthetic method for 1, the total synthesis of 2 was also first accomplished. The synthetic 1 and 2 were identical with the natural 1 and 2 with respect to the chemical and physical properties.
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Research Products
(14 results)
