Enantioselective synthesis of 12-amino alkylidenecyclopentenone prostaglandins.
An enantioselective synthesis of new 12-amino alkylidenecyclopentenone prostaglandins is reported. The key step of the synthesis involved a [3.3] sigmatropic rearrangement of an asymmetric allylic cyanate to elaborate an asymmetric 5-amino-1,6-diene which was further transformed into cyclopentenone by successive ring-closing metathesis reaction catalyzed by the Grubbs reagent and one-pot oxidation. A palladium-catalyzed cross-coupling reaction on a 5-iodo-1,5-diene allowed the synthesis of prostanoids with variable Rw side chains. These new compounds exhibit high cytotoxic activities.
Roulland
Emmanuel
E
UMR 176 CNRS-Institut Curie, Section de Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
Monneret
Claude
C
Florent
Jean-Claude
JC
Bennejean
Caroline
C
Renard
Pierre
P
Léonce
Stéphane
S
D000818:Animals; D002384:Catalysis; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium; D011454:Prostaglandins A / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011455:Prostaglandins A, Synthetic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011454:Prostaglandins A; D011455:Prostaglandins A, Synthetic; C469647:TEI9826; C469646:punaglandin III; D010165:Palladium; C057741:clavulone II; C048481:9-oxo-15-hydroxy-delta 7,10,13-prostatrienoic acid methyl ester