2007 Fiscal Year Final Research Report Summary
Studies on Determination of Absolute Stereochemistry of Stereochemically Undefined Natural Polyether Macrolides by NMR Comparison with Synthetic Macrocyclic Models
| Project/Area Number |
18510179
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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 |
Living organism molecular science
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| Research Institution | Hokkaido University |
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Principal Investigator |
FUJIWARA Kenshu Hokkaido University, Fac. of Sci., Associate Professor (20222268)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Goniodomin A / Bioactive natural products / Determination of stereochemistry / Polyether macrorides / Macrocyclization / Macrocyclic analogues / Confromational restriction / NMR analysis |
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| Research Abstract |
To confirm the absolute stereochemistry of goniodomin A, a structurally undefined polyether macrolide, its total synthesis was planned and investigated. Goniodomin A was isolated from dinoflagellate Alexandrium hiranoi as an antifungal agent by Murakami in 1988. Later, its particular bioactivities, such as modulation of actomyosin ATPase activities, increasing the filamentous actin content of human astronoma cells, and antiangiogenic activity via inhibition of actin reorganization in endothelial cells, were found. Although its detailed NMR data and unique planer structure featured by a 32-membered macrolactone including 5- and 6-membered cyclic ethers (the A-, D- and E-ring parts), a spirocyclic acetal (the BC-ring part), and a 6-membered cyclic hemiacetal (the F-ring part) were reported, the stereochemistry of goniodomin A was unclear. From this research project, determination of the relative configurations of the A-, DE-, F-rings of goniodomin A and their partial synthesis have been achieved. The followings efforts were also made: (1) some candidate relative configurations for the ABC-ring of goniodomin A were predicted from the NMR data of the natural product reported by Murakami; (2) three model compounds having the predicted configurations were synthesized; (3) when NMR data of natural goniodomin A were compared with those of model compounds, one of the models showed almost identical data except the coupling constant between H15 and H14, suggested that the natural ABC-ring was a C15 epimer of the model; (4) after several experiments, it was also suggested that the natural BC-ring had a particular configuration that could only be realized by the presence of the macrolide framework; (5) a synthetic method for the CDE-ring segment having proper stereochemistry was developed.
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