1999 Fiscal Year Final Research Report Summary
Highly enantioselective synthesis of anti-cancer epothilone and its stereoisomers
| Project/Area Number |
10640525
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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 | Kochi University |
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Principal Investigator |
KIYOOKA Syn-ichi Faculty of Science, Kochi University Professor, 理学部, 教授 (00036584)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Asymmetric aldol reaction / Chiral borane / Epothilones / Macrolides / Acyclic stereoselection |
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| Research Abstract |
The asymmetric total synthesis of epothilones was carried out by the strategy based on the chiral oxazaborolidinone-promoted asymmetric aldol reaction. First, the asymmetric synthesis of the C1-C9 fragment which is comprised of the condensed asymmetric centers of epothilones was examined. The first stereocenter was highly controlled by our asymmetric aldol technique as to give 98% ee. However, the asymmetric aldol reaction on the aldehyde, which is possessing bulky substituents at the quaternary carbon, did not succeed for the construction of the expecting stereochemistry, even if what kind of conditions was examined (Tetrahedron Lett, 1999). From this research, it was possible to determine the limitation of the chiral oxazaborolidinone-promoted asymmetric aldol reaction. Thus, the stereoselective construction of C6-C7 bond was changed in achieving the diastereoselective condensation using LDA by Schinzer et al. The ketone available for the aim was successfully synthesized by our strategy. While the asymmetric synthesis from the heterocyclic side of epothilones is examined and the first introduction of chiral center has succeeded as expected by the asymmetric aldol reaction. At present the extension of the chain is being examined. In the meantime, the stereoselective construction of the tri-substituted epoxides was also established (Tetrahedron Lett.). Though the total synthesis of epothilones has not been achieved yet the completion will be close in the near future.
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