Synthesis of 4-aryl-2-pyrrolidones and beta-aryl-gamma-amino-butyric acid (GABA) analogues by Heck arylation of 3-pyrrolines with arenediazonium tetrafluoroborates. Synthesis of (+/-)-rolipram on a multigram scale and chromatographic resolution by semipreparative chiral simulated moving bed chromatography.
We report herein a new, practical, and economic synthesis of the phosphodiesterase inhibitor Rolipram on a multigram scale as well as the synthesis of new 4-aryl pyrrolidones and beta-aryl-gamma-amino butyric acids (GABA derivatives) employing an efficient Heck-Matsuda arylation of 3-pyrroline with aryldiazonium tetrafluoroborates. Racemic Rolipram was resolved into its enantiomers using chiral simulated moving bed chromatography having the low-cost microcrystalline cellulose triacetate as a chiral stationary phase.
Garcia
Ariel L L
AL
Chemistry Institute, State University of Campinas-UNICAMP, 13084-971, Campinas, São Paulo, Brazil.
Carpes
Marcos J S
MJ
de Oca
Antonio C B M
AC
dos Santos
Marco A G
MA
Santana
César C
CC
Correia
Carlos Roque D
CR
D001881:Borates / Q000737:chemistry* / Q000378:metabolism; D002852:Chromatography, Ion Exchange / Q000379:methods; D003979:Diazonium Compounds / Q000737:chemistry / Q000378:metabolism; D017611:Fluorine Compounds / Q000737:chemistry* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis*; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D020889:Rolipram / Q000138:chemical synthesis*; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D001881:Borates; D003979:Diazonium Compounds; D017611:Fluorine Compounds; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C002195:3,4-dehydroproline; D005680:gamma-Aminobutyric Acid; D011392:Proline; D020889:Rolipram