Parallel synthesis of prostaglandin E1 analogues.
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.
Dragoli
D R
DR
Department of Chemistry, University of California, Berkeley 94720, USA.
Thompson
L A
LA
O'Brien
J
J
Ellman
J A
JA
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
D000577:Amides; D007202:Indicators and Reagents; D018078:Receptors, Prostaglandin E; D000527:Alprostadil