2005 Fiscal Year Final Research Report Summary
Development of Novel Tandem Cyclization Using Palladium Catalyst and Its Application to the Synthesis of Natsural Products
| Project/Area Number |
16590004
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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 | Toyama University |
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Principal Investigator |
HIRAI Yoshiro Toyama University, Faculty of Science, Professor, 理学部, 教授 (70111747)
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| Project Period (FY) |
2004 – 2005
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| Keywords | tandem cyclization / hemiacetal intermediate / palladium (II) catalyst / hetero-cyclization / 5-epi-prelactone C / spiroketal / spirofungin A / spirofungin B |
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| Research Abstract |
The polysubstituted γ-lactone structure can be found in many natural products, particularly polyketide macrolide producing microorganisms. It is a very important to develop synthetic methodology for the streo-selective construction of the γ-lactone structure.
We recently developed a cyclization via a hemiacetal intermediate using palladium (II) cartalyst and found a stereo selective construction of trisubstituted tetrahydropyran.
In connection with the palladium (II) catalyzed hetero-cyclization, we applied the method to synthesis of a natural product having a γ-lactone structure. The cyclization of the aldehyde containing the secondary alcohol using PdCl_2(Ph_3CN)_2 in THF in the presence of alcohol gave the cyclized product, stereo-selectively. 5-Epi-prelactone C was also synthesized by the similar method.
On the other hand, the spiroketal moiety is one of the most important constituents of polycyclic ethers and polypropionates. These spiroketal compounds exhibit interesting physiological activities. Therefore stereo-selective construction of the spiroketal structure is very important in organic synthesis.
Then, we studied the construction of spiroketal structure by intramolecular tantem cyclization using palladium (II) cartalyst.
Treatment of 1,11-dihydroxy-7-oxo-5-phenyl-2-undecene with 10 mol% PdCl_2(Ph_3CN)_2 in THF afforded the spiroketal compound as a single stereo-isomer.
Next, we tried the synthesis of spirofungin A and B, novel polyketide-type antibiotics isolated from Steptomyces violaceusiger Tu 4113. The key tandem cyclization of the substrate (the dihydroxyketone compound) was achieved successfully by treatment with PdCl_2(Ph_3CN)_2 to give a spiroketal compound, which was the important intermediate for the synthesis of spirofungin A
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