| Project/Area Number |
08457579
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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 |
Chemical pharmacy
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
NAKAGAWA Masako CHIBA UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (40009171)
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| Co-Investigator(Kenkyū-buntansha) |
KAWATE Tomohiko CHIBA UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,RESEARCH ASSOCIATE, 薬学部, 助手 (50195111)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Asymmetric Synthesis / manzamine A / dynemicin A / Diels-Alder reaction / PPMP / Asymmetric Pictet-Spengler reaction / VSR / Antitumor Alkaloid / アゾシン環 / イルシナールA / Diels-Alder反応 / X線結晶構造解析 / Vsr / DNA修復酵素 / vsr発現ベクター / キラルルイス酸 / 2-キノロン / ケトン合成 |
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| Research Abstract |
I.Enantioselective total synthetic approaches to manzamine A and dynemicin A
I) Synthesis of the tetracyclic core of manzamine A (1) was achieved via Diels-Alder reaction of the dihydropyridinones. Conversion of the two D-A products to the key tricyclic ketone was conducted through a conventional pathway as well as a new pathway developed.
2) The highly stereoselective synthesis of the optically active tetracyclic core of Manzamine A was achieved via the Diels-Alder reaction of dihydropyridinone, derived from L-serine, with siloxydienes, followed by sequential new and conventional pathways.
3) Preparation of the 1-methoxycarbonyl-3-phenylthio-2-quinolinone from dihydro-2-quinolinone and its Diels-Alder reaction with 2-trimethylsilyloxy- 1, 3-butadiene and 2-TMSO- 1, 3-pentadiene under Lewis acid catalyst was developed. Conversion of the D-A adduct to 9-phenanthridinone ketal will open a new synthetic route to a dynemicin A core structure.
4). We found an efficient synthesis of a, beta-unsaturated ketones by the reaction of acid chlorides with trialkylaluminum (1/3 mole equiv) in the presence of AlC13 (I mol equiv).
II.Both L-threo and D-ervthro-1-phenyl-2-palmitoylamino-3-morpholino- 1-propanol (PPMP) and the decanoyl derivative (PDMP) were synthesized stereselectively from L-serine.
III.The crystal structure of Vsr endonuclease was determined by X-ray analysis.
IV.The first example of a reagent-controlled enantioselective Pictet-Spengler reaction was achieved. Using diisopinocampheylchloroborane as a chiral Lewis acid catalyst, the Pictet-Spengler reaction of Nb-hydroxytryptamine with aldehydes gave the corresponding 2-hydroxytetrahydro-beta-carbolines in up to 90% ee. The enantioselective Pictet-Spengler reaction catalyzed by chiral binaphthol-derived Brphindted acid-assisted Lewis acids, with up to 91% ee, was also achieved.
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