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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2005-4-12
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pubmed:abstractText |
A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to 1 was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-3263
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pubmed:author |
pubmed-author:ChenCheng-yiCY,
pubmed-author:ChenWeirongW,
pubmed-author:DagneauPhilippeP,
pubmed-author:FreyLisa FLF,
pubmed-author:GrabowskiEdward J JEJ,
pubmed-author:MarcantonioKaren MKM,
pubmed-author:O'SheaPaul DPD,
pubmed-author:ReamerRobert ARA,
pubmed-author:RoyAmélieA,
pubmed-author:TanLushiL,
pubmed-author:TillyerRichard DRD,
pubmed-author:VigoC BCB,
pubmed-author:ZhaoDalianD
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3021-30
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15822960-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:15822960-Combinatorial Chemistry Techniques,
pubmed-meshheading:15822960-Cyclic N-Oxides,
pubmed-meshheading:15822960-Cyclic Nucleotide Phosphodiesterases, Type 4,
pubmed-meshheading:15822960-Enzyme Inhibitors,
pubmed-meshheading:15822960-Magnetic Resonance Spectroscopy,
pubmed-meshheading:15822960-Molecular Structure,
pubmed-meshheading:15822960-Pyridines,
pubmed-meshheading:15822960-Stereoisomerism
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pubmed:year |
2005
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pubmed:articleTitle |
Practical asymmetric synthesis of a potent PDE4 inhibitor via stereoselective enolate alkylation of a chiral aryl-heteroaryl secondary tosylate.
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pubmed:affiliation |
Department of Process Research, Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval, Québec H9R 4P8, Canada. paul_oshea@merck.com
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pubmed:publicationType |
Journal Article
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