1996 Fiscal Year Final Research Report Summary
Studies on the development of new, practical synthetic methods for the synthesis of physiologically active compounds related to vitamin D
| Project/Area Number |
06555281
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Synthetic chemistry
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| Research Institution | Okayama University |
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Principal Investigator |
SAITO Seiki Okayama University, Faculty of Engineering, Professor, 工学部, 教授 (60033239)
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| Co-Investigator(Kenkyū-buntansha) |
NITTA Issei Fuji Pharmaceutical Industry, Research Manager, 研究部長
MANDAI Tadakatsu Kurashiki University of Science and the Arts, College of Science and Industrial, 大学産業技術学部, 教授 (80131621)
ISHIKAWA Teruhiko Okayama University, Faculty of Engineering, Instructor, 工学部, 助手 (10263617)
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| Project Period (FY) |
1994 – 1996
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| Keywords | Vitamin D / A-Ring asym, syn. / alpha-Silyl allyl anion / Peterson olefination / Intram.nitril oxide cycloadd. / C,D-Ring asym.syn. / Asym.intram.W.-E.Reac. |
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| Research Abstract |
The subject of this research is to establish versatile methods for the synthesis of Vitamin D and related compounds which can be submitted to physiological tests to systematically investigate the structure-activity relationship. The research takes advantage of convergent strategy and covers following categories : the development of novel methods for the asymmetric synthesis of C,D- and A-rings, which can be coupled by unprecedented methodology featuring nature-friendly and short-cut processes. The C,D-ring synthon has been prepared in 98.3 %de based on diastereoselective intramolecular Wadsworth-Emmons reaction relying on phenylmenthyl group as a chiral auxiliary. The optically pure A-ring synthon has been in hand efficiently by means of intramolecular 1,3-dipolar cycloaddition reaction of optically pure omega-olefinic dihydroxylnitriloxide which can be derived conveniently from optically pure ethyl (3S) -3,4-dihydroxybutanoate derivative available in multigram quantities from natural L-malic acid. Also, though remained at the stage of model reaction, it has been shown that Peterson-type olefination reaction between alpha, beta-unsaturated aldehyde and allylsilane may be promising for the forthcoming coupling process of the A-ring synthon with C,D-ring synthon. The methods developed in this research seem applicable to the synthesis of structurally diversed vitamin D derivatives. We will get involved in this research for the time being whcih would hopefully make the methods much better in terms of synthetic steps involved or availability of starting chiral templates for the C,D-ring synthon.
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