Total synthesis of (15R)- and (15S)-F(2t)-isoprostanes by a biomimetic process using the cyclization of acyclic dihydroxylated octa-5,7-dienyl radicals.
We report a new route to F(2t)-IsoP (formerly named 8-epi-PGF(2alpha)) using a biomimetic radical cyclization of a highly functionalized C20 precursor. The strategy employed gives a beta-hydroxy free radical followed by molecular oxygen trapping, which is an unusual method for quenching carbon free radicals. We observed the formation of unique diastereoisomers (15R)- and (15S)-F(2t)-IsoP. This result is consistent with a strong stereoelectronic control associated with a steric effect initiated by the side chains alpha and omega on the cyclopentane ring.
Durand
Thierry
T
Laboratoire de Chimie Biomoléculaire et Interactions Biologiques, associée au CNRS (UMR 5074), and Université Montpellier I, Faculté de Pharmacie, 15 Av. Charles Flahault, B.P. 14 491, F-34093 Montpellier Cedex 5, France.
Guy
Alexandre
A
Vidal
Jean-Pierre
JP
Rossi
Jean-Claude
JC
D003500:Cyclization; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000138:chemical synthesis*; D005609:Free Radicals / Q000737:chemistry; D018716:Molecular Mimicry; D013237:Stereoisomerism
D028441:F2-Isoprostanes; D005609:Free Radicals; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost