Catalytic enantioselective synthesis of (-)-prostaglandin E1 methyl ester based on a tandem 1,4-addition-aldol reaction.
Catalytic enantioselective 1,4-additions and tandem 1,4-addition-aldol reactions of dialkylzinc reagents to cyclopentene-3,5-dione monoacetals in the presence of an in situ generated Cu(OTf)(2)/chiral phosphoramidite catalyst result in highly functionalized cyclopentane building blocks with ee's up to 97%. A new synthesis of cyclopentene-3,5-dione monoacetals is presented as well as its use in a tandem 1,4-addition-aldol protocol for the catalytic asymmetric total synthesis of (-)-PGE(1) methyl ester. This synthesis represents a new approach to this class of natural products. By using only 3 mol % of an enantiomerically pure catalyst in the key step, the absolute configurations at three stereocenters of the basic structure of the PGE(1) are established at once.
Arnold
Leggy A
LA
Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Naasz
Robert
R
Minnaard
Adriaan J
AJ
Feringa
Ben L
BL
D000107:Acetylation; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation
D007202:Indicators and Reagents; C439321:prostaglandin E1 methyl ester; D000527:Alprostadil