The first synthetic studies on pestalotiopsin A. A stereocontrolled approach to the functionalised bicyclic core.
Pestalotiopsin A is a structurally unique, caryophyllene-type sesquiterpene which has shown immunosuppressive activity and cytotoxicity in preliminary assays. A stereocontrolled approach to the functionalised 2-oxabicyclo[3.2.0]-heptane core of pestalotiopsin A is described. This constitutes the first synthetic studies on pestalotiopsin A. Our approach includes a samarium(II)-mediated 4-exo-trig cyclisation and a trans-lactonisation process triggered by the addition of alkylytterbium reagents to a cyclobutanone intermediate. Further manipulation provides access to advanced intermediates which are excellent precursors for the future construction of the final ring of the target.
Johnston
Derek
D
Department of Chemistry, Joseph Black Building, University of Glasgow, Glasgow, UK G12 8QQ.
Couché
Emmanuel
E
Edmonds
David J
DJ
Muir
Kenneth W
KW
Procter
David J
DJ
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D003503:Cyclobutanes / Q000737:chemistry; D006536:Heptanes / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D015394:Molecular Structure; D012493:Samarium / Q000737:chemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D003503:Cyclobutanes; D006536:Heptanes; D007202:Indicators and Reagents; D012717:Sesquiterpenes; C430595:pestalotiopsin A; D012493:Samarium