1890-99-9Relevant articles and documents
Synthesis, optical resolution, absolute configuration, and osteogenic activity of cis-pterocarpans
Goel, Atul,Kumar, Amit,Hemberger, Yasmin,Raghuvanshi, Ashutosh,Jeet, Ram,Tiwari, Govind,Knauer, Michael,Kureel, Jyoti,Singh, Anuj K.,Gautam, Abnish,Trivedi, Ritu,Singh, Divya,Bringmann, Gerhard
, p. 9583 - 9592 (2013/01/16)
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. The Royal Society of Chemistry 2012.
Biosynthesis of the A/B/C/D-Ring System of the Rotenoid Amorphigenin by Amorpha fruticosa Seedlings
Bhandari, Prabha,Crombie, Leslie,Daniels, Peter,Holden, Ian,Bruggen, Nicholas Van,Whiting, Donald A.
, p. 839 - 850 (2007/10/02)
With phenylalanine as the starting point, the biosynthesis of the characteristic rotenoid A/B/C/D-ring system of amorphigenin is studied using Amorpha fruticosa seedlings.The course of the biosynthesis can be divided into four phases represented by the bordered and interconnecting Schemes 1, 3, 6 and 7 which summarise the Chalcone-Flavanone Phase, the Flavanone-Isoflavone Phase, the Hydroxylation/Methoxylation Phase and the Rotenoid Phase.By using an INADEQUATE NMR experiment involving the administration of acetate, the type of folding forming ring-D isdemonstrated by 13C-13C coupling and is interpreted as involving a polyketide containing a glutaconate segment which cyclises by a Claisen condensation.The resulting chalcone is cyclised, enzymically and stereospecifically, to 4',7-dihydroxyflavanone.The latter flavanone undergoes aryl migration, in a manner similar to that found in isoflavone biosynthesis, to give 7-hydroxy-4'-methoxyisoflavone.Possible mechanisms for the flavanone-isoflavone rearrangement are discussed, including a proposal that the initiating step involves attack on ring-A and is similar to the first stage of the aromatic hydroxylation of tyrosine to dopa.Although possessing no 4'-hydroxy group in ring-A, the mechanism is also applicable to the recently discovered rotenoids of the Boerhaavia and Iris type, and it provides an explanation for the biogenesis of natural spirobenzocyclobutanes from dihydroeucominoids.Six suitably substituted isoflavonoids labelled with 13C or 3H are synthesized and are used to show that the next hydroxylation (and probably methylation) involves C-3' rather than C-2' in 7-hydroxy-4'-methoxyisoflavone.Whilst the methylations involveS-adenosylmethionine, the hydroxylating enzymes are probably very similar to the flavanone-isoflavone-rearranging enzyme.The closure of ring-B to form finally the rotenoid system probably involves conjugate addition of a methoxyl radical.Prenylation and oxidative modifications are characteristically late-stage processes.
