Catalytic one-pot synthesis of [5.5.5.6]fenestrane systems via a dicobalt octacarbonyl-catalyzed tandem cycloaddition of dienediynes.
Catalytic one-pot synthesis of fenestrane derivatives from dienediynes was developed: fenestranes were synthesized in high yields by a dicobalt octacarbonyl-catalyzed tandem cycloaddition of dienediynes.
General approach for the synthesis of polyquinenes via the weiss reaction XIII. Aldol approach to fenestranes.
Abstract The acid-catalyzed intramolecular aldol cyclization (HCl/THF; Ac 2 O) of diketodialdehyde 5 under conditions of thermodynamic (equilibration) control furnished the 8α,12β-diacetoxytetracyclo[5.5.1.04,13.010,13]tridecane-2,6-dione 6 to provide a new entry into [5.5.5.5]fenestanes. The analogous conversion of bisaldehyde 14 into the 2,8-diacetoxytetracyclo[7.5.1.05,15.012,15]pentadecane-10,14-dione system was not successful.
Pharmacokinetics and Metabolism of 14C-Brivaracetam, a Novel SV2A Ligand, in Healthy Subjects
This study was designed to investigate the human absorption, disposition, and mass balance of 14C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of 14C-brivaracetam (150 mg, 82 μCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with Cmax of 4 μg/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non–cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.