1994 Fiscal Year Final Research Report Summary
Synthetic Study on anti-PAF active S,N-containing Heterocycles
| Project/Area Number |
05640620
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Organic chemistry
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| Research Institution | Kwansei Gakuin University |
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Principal Investigator |
TANABE Yoo Kwansei Gakuin University, School of Science, Associate Professor, 理学部, 助教授 (30236666)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Anti-PAF activity / S,N-containing Heterocycles / Antagonist / Silyl compound / tetrabutylammonium fluoride / thiazolidin-4-one / Stereoselective synthesis / SAR |
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| Research Abstract |
Since the discovery of the platelet activating factor (PAF) , a number of investigations have been devoted to developing it for the medical applications. Along with them, increasing interest has centered on the anti-PAF active agent (PAF antagonist) , and so their research is currently the most challenging problem in pharmacology. As part of our continuing program in search of biologically active sulfur and nitrogen containing heterocycles, we made the synthetic study on the following subjects : (1) Reactivity and relative stereoselectivity (cis/trans) in the construction of thiazolidin-4-ones through the cyclo-condensation reaction ; (2) Relative stereoselectivity in the allylation reaction of the 5-position of the thiazolidin-4-one ; (3) Syntheses of four optically active isomers of the two representative compounds to clarify the stereostructure-activity relationship ; (4) Regioselective epimerization of the 5-position of the thiazolidin-4-ones promoted by bases ; (5) Highly stereoselective synthesis of the anti-platelet activating factor, 4-thiazolidinones using silyl derivatives of 2-mercaptoalkanoic acids ; and (6) Syntheses of perhydro-1,3,4-thiadiazin-5-ones and 3- (arylamino) thiazolidin-4-ones by the regioselective cyclo-condensation of 2-sulfanylalkanoic acids or their silyl esters with methyl and phenyl hydrazones.
These results prompted us to extend general synthetic studies "effectively utilizing the activation of the silicon-heteroatom bond ; (1) Mild, effective and selective method for the silylation of alcohols using silazanes promoted by catalytic tetrabutylammonium fluoride ; (2) Mild and practical method for the silylation of alcohols using hydrosilanes and disilanes promoted by TBAF catalyst ; and (3) Direct and electrophilic preparation of alpha-thiocyanatoketones and aldehydes using thiocyanatotrimethylsilane and sulfuryl chloride.
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