title: Parallel synthesis of prostaglandin E1 analogues.
abstract: The first demonstration of the rapid parallel synthesis of diverse prostaglandin derivatives is reported. Upper (alpha-) side chain diversity was introduced to core 1 via the parallel Suzuki coupling of hydroborated alkenes. Conversion to the enones 3 and 9 was followed by the addition of the lower (omega-) side chains as higher-order cuprates 4. Upper side chains incorporating an N-acylsulfonamide protecting group were further transformed into prostaglandin amide analogues. Cleavage from support with HF/pyridine followed by scavenging provided 26 prostaglandin E1 analogues in high purity.
authors.affiliation: Department of Chemistry, University of California, Berkeley 94720, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Dragoli
authors.forename: L A
authors.initials: LA
authors.lastname: Thompson
authors.forename: J
authors.initials: J
authors.lastname: O'Brien
authors.forename: J A
authors.initials: JA
authors.lastname: Ellman
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000577:Amides; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D015195:Drug Design; D007202:Indicators and Reagents; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D007202:Indicators and Reagents; D018078:Receptors, Prostaglandin E; D000527:Alprostadil