2006 Fiscal Year Final Research Report Summary
Synthetic Studies of Natural Products Using By a Chelation Controlled Claisen Rearrangement
| Project/Area Number |
17590009
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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 |
Chemical pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
ISHIHARA Jun Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (80250413)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Susumi Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院医歯薬学総合研究科, 教授 (20143000)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Claisen rearrangement / Remote Stereo-induction |
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| Research Abstract |
Synthesis of natural products often requires various methods for control of stereochemistry of complicated carbon-carbon framework. Recently we found that the Ireland-Claisen rearrangement of Li-enolate of the modeled ester with Me_2SiCl_2 in toluene afforded the desired limonoid framework stereoselectively. The coordination of the chlorodimethylsilyl group would be attributed to the predominance of the Z-silyl ketene acetal, generating the desired rearranged product. This remote induction of stereochemistry was the first example by chelation of the chlorodimethylsilane to adjacent lactone carbonyl group. In this study, we developed this type of remote controlled Claisen rearrangement reactions to apply to synthesis of clutiolide, modified labdane diterpene derived from Euphorbia speicies in Ethiopia. This natural product has similar structure to saudin, which shows to possess in vivo noninsulin dependent hypoglycemic activity. We planned to synthesize of cultiolide using by the remote
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controlled Claisen rearrangement. The precursor of rearrangement was prepared by esterification of allyl alcohol and bicyclic acid, which was readily synthesize by intramolecular Diels-Alder reaction. The Claisen rearrangement of allylic ester with LHMDS Me_2SiCl_2 in toluene proceeded in a excellent selectivity to afford the desired skeleton with three contiguous stereogenic centers in 55% yield. On the other hand, we also investigated another unique Claisen rearrangement. The Claisen rearrangement or α-bromo ester has been known as Reformatsky-Claisen rearrangement, however it is not so often to apply this methodology to natural products synthesis, even though it can be performed under base-free, mild condition. We found that the Reformatsky-Claisen rearrangement of allylic cyclohexyl ester with In, InCl_3, TMSCl, and Et_3N provided the rearranged product with a quarternary center in a good yield. Since the late-period metal such as indium is capable to coordinate to oxygen atom, this Reformatsky-Claisen rearrangement has also possibility to be applied to remote chelation controlled reaction. Less
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