The conjugate addition-Peterson olefination reaction for the preparation of cross-conjugated cyclopentenone, PPAR-gamma ligands.
5-Alkylidenecyclopent-2-enones 15a-q may be prepared via a conjugate addition-Peterson olefination sequence, best achieved in one-pot, using exo-2-trimethylsilyl-3a,4,7,7a-tetrahydro-4,7-methanoinden-1-one 12, followed by a retro-Diels-Alder reaction. The geometry of the exocyclic alkene may be controlled according to the use of organometallic species in the conjugate addition step; organocuprate reagents are found to selectively lead to the formation of E-exocyclic alkene adducts, whereas Grignard reagents favour the formation of Z-alkenyl isomers. The use of enantiomerically enriched 12, accessed from an asymmetric Pauson-Khand reaction, affords the corresponding enantioenriched 5-alkylidenecyclopent-2-enones and this approach is exemplified by the short, stereoselective total syntheses of two cyclopentenone phytoprostanes 51 and 13,14-dehydrophytoprostane J1 65. The ability of this family of synthetic compounds to activate the peroxisome proliferator activated receptor-gamma is reported.
Iqbal
Mazhar
M
Department of Chemistry, University of Liverpool, Liverpool, UKL69 7ZD.
Duffy
Patricia
P
Evans
Paul
P
Cloughley
George
G
Allan
Bernard
B
Lledó
Agustí
A
Verdaguer
Xavier
X
Riera
Antoni
A
D000475:Alkenes / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D003517:Cyclopentanes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D047495:PPAR gamma / Q000819:agonists*
D000475:Alkenes; D003517:Cyclopentanes; D008024:Ligands; D047495:PPAR gamma; C013905:cyclopentenone