title: Synthesis, optical resolution, absolute configuration, and osteogenic activity of cis-pterocarpans.
abstract: A convenient synthesis of natural and synthetic pterocarpans was achieved in three steps. Optical resolution of the respective enantiomers was accomplished by analytical and semi-preparative HPLC on a chiral stationary phase. For medicarpin and its synthetic derivative 9-demethoxymedicarpin, the absolute configuration was confirmed by a combination of experimental LC-ECD coupling and quantum-chemical ECD calculations. (-)-Medicarpin and (-)-9-demethoxymedicarpin are both 6aR,11aR-configured, and consequently the corresponding enantiomers, (+)-medicarpin and (+)-9-demethoxymedicarpin, possess the 6aS,11aS-configuration. A comparative mechanism study for osteogenic (bone forming) activity of medicarpin (racemic versus enantiomerically pure material) revealed that (+)-(6aS,11aS)-medicarpin (6a) significantly increased the bone morphogenetic protein-2 (BMP2) expression and the level of the bone-specific transcription factor Runx-2 mRNA, while the effect was opposite for the other enantiomer, (-)-(6aR,11aR)-medicarpin (6a), and for the racemate, (±)-medicarpin, the combined effect of both the enantiomers on transcription levels was observed.
authors.affiliation: Division of Medicinal and Process Chemistry, CSIR - Central Drug Research Institute, Lucknow 226001, India. atul_goel@cdri.res.in
authors.forename: Atul
authors.initials: A
authors.lastname: Goel
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Hemberger
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Raghuvanshi
authors.forename: Ram
authors.initials: R
authors.lastname: Jeet
authors.forename: Govind
authors.initials: G
authors.lastname: Tiwari
authors.forename: Michael
authors.initials: M
authors.lastname: Knauer
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kureel
authors.forename: Anuj K
authors.initials: AK
authors.lastname: Singh
authors.forename: Abnish
authors.initials: A
authors.lastname: Gautam
authors.forename: Ritu
authors.initials: R
authors.lastname: Trivedi
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050071:Bone Density Conservation Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D002236:Carbohydrate Conformation; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D036343:Pterocarpans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: C525720:Bmp2 protein, rat; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D036343:Pterocarpans; C493717:Runx2 protein, rat