79563-87-4Relevant academic research and scientific papers
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.
Metabolic fate of the new cardiotonic denopamine in animals. 1st Communication: Absorption, distribution and excretion in the rat, rabbit and dog
Naito,Furuuchi,Yamada,Otsuka,Harigaya
, p. 643 - 651 (2007/10/02)
Absorption, distribution and excretion of (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino] ethanol (denopamine, TA-064) a new positive inotropic agent, were studied after oral and intravenous administration of 3H- or 14C-denopamine (5 mg/kg) to different animal species. After oral administration to rats, rabbits and dogs, the time to attain the peak and the maximum concentration of the plasma levels of radioactivity were about 15 min, 4 μg eq./ml in rats, 15-45 min, 8 μg eq./ml in rabbits and 2-4 h, 2 μg eq./ml in dogs, respectively. The plasma denopamine levels in dogs reached the peak (0.34 μg/ml) at 0.5-3 h after administration, and thereafter gradually decreased with half-lives of 1.6-3.1 h. Following oral administration to rats, the amounts remaining of the parent compound in the digestive tract at 0.5 and 3 h after administration were about 27 and 2% of the dose administered, respectively. This indicated that the compound was rapidly and almost completely absorbed from the intestinal tract. When 3H-denopamine was orally administered to rats, cumulative excretion of radioactivity in the urine and feces within 24 h were about 60 and 32% of the dose, respectively. Almost 100% of the dose were recovered from the urine and feces within 120 h. About 50% of the dose administered were excreted in the bile within 24 h. The occurrence of enterohepatic circulation was indicated in rats. Distribution of radioactivity was investigated in rats by means of whole body autoradiography and the tracer technique. Radioactivity in various tissues was highest at 15-30 min after administration and distributed throughout the body, except for the central nervous system. The highest radioactivity was found in the liver, kidney, lung and blood, while the heart showed moderate radioactivity. Disappearance of radioactivity from the body was relatively rapid, and radioactivity was extremely low in all the organs at 24 h after administration, except that slight radioactivity was observed in the testis and moderate in the contents of the digestive tract. The distribution pattern of radioactivity following intravenous administration was similar to that following oral administration. The peak levels of unchanged compound in various tissues of rats were also noted at 15 min after administration. A good correlation was observed between the blood and heart levels of unchanged denopamine. In vitro percent binding of denopamine to plasma protein was 87% in rabbits, 52% in rats, 43% in human and 35% in dogs. At 15 and 60 min after oral administration, percent binding of 3H-denopamine and/or its metabolites to the rat plasma was about 1/2 of that of denopamine in vitro.
