Mechanistic and Synthetic Implications of the Diol-Ritter Reaction: Unexpected Yet Reversible Pathways in the Regioselective Synthesis of Vicinal-Aminoalcohols.

The Ritter reaction of 1,2-diolmonoesters with nitriles to 1- vic-amido-2-esters proceeds through dioxonium and nitrilium cation intermediates. To provide the basis for the reaction mechanism, novel forms of these cations were isolated, characterized, and studied by spectroscopic methods and single crystal X-ray analysis. Ground and transition state energies were determined both experimentally and theoretically.

Studies of the extraction of bilirubin from human amniotic fluid.

The recovery of unconjugated bilirubin from human amniotic fluid was studied using dichloromethane, chloroform/isopropanol (3:1 vol/vol), and chloroform/ methanol (3:1 vol/vol) extraction of human amniotic fluid that had been supplemented with bilirubin at various concentrations. Results were compared with those obtained with conventional chloroform extraction. Mean recoveries were found to be only 28% for chloroform and 25% for dichloromethane.

Synthesis of biologically active amines via rhodium-bisphosphite-catalyzed hydroaminomethylation.

[reaction: see text] We report the use of a highly regioselective rhodium-bisphosphite catalyst for olefin hydroaminomethylation. This catalyst system was successfully applied in the synthesis of two biologically active tertiary amines, ibutilide and aripiprazole.

Studies of the inhibition of serum pseudocholinesterase activity in vitro by commonly used drugs.

We studied the effect of 17 commonly used drugs, including prescription and over-the-counter medications, on the activity of serum pseudocholinesterase (PCE) in vitro. Normal pooled human serum was incubated for 120 minutes at 37 degrees C with therapeutic serum concentrations of prescription and over-the-counter drugs, and the postincubation PCE activity was measured. Morphine, quinidine, and thioridazine depressed PCE activity by more than 5% while no or negligible effect was noted following incubation with acetaminophen, chlordiazepoxide, chlorpromazine, desipramine, doxepin, imipramine, methamphetamine, nortriptyline, phenobarbital, phenytoin, procainamide, salicylic acid, theophylline, and valproic acid.

Valproic acid binding to human serum and human placenta in vitro.

The binding characteristics of the antiepileptic agent and teratogen valproic acid for human serum and human placenta were investigated utilizing equilibrium dialysis of the drugs in serum and in homogenates of whole placenta so that the transplacental transfer of the drug could be better defined. A low-capacity, high-affinity binder and a high-capacity, low-affinity binder for valproic acid were found in serum. However, there was only minimal, nonspecific binding of the drug to placenta.

The effect of lovastatin and thioridazine on the degradation of cocaine in human serum in vitro.

The effect of lovastatin and thioridazine on the degradation of cocaine in human serum was studied by incubating therapeutic and toxic concentrations of either drug with cocaine in human serum at 37 degrees C. Without these other drugs, cocaine concentrations decreased by an average of 88% in 120 minutes. Lovastatin at all concentrations studied showed a negligible effect on the degradation of cocaine in human serum and did not alter the pseudocholinesterase activity of the serum.

The binding of acetaminophen, lidocaine, and valproic acid to human milk.

The binding of acetaminophen, lidocaine, and valproic acid to pooled normal mature human milk was studied in vitro by using equilibrium dialysis. Scatchard analysis revealed high-affinity, low-capacity binding for acetaminophen (Ka [affinity constant of association], 1.47 x 10(4) L/mol; Bo [concentration of binding sites], 9.

Gentamicin and tobramycin binding to human serum in vitro.

The binding of gentamicin and tobramycin to human serum was studied in vitro using equilibrium dialysis of pooled human serum supplemented to various concentrations of either drug. Only minimal and variable non-specific binding was noted for each drug: gentamicin, less than 15% and tobramycin, less than 30%. Conventional Scatchard analysis conducted over an array of drug concentrations failed to identify any specific binding proteins.

The binding of selected therapeutic drugs to human serum alpha-1 acid glycoprotein and to human serum albumin in vitro.

The binding of acetaminophen, lidocaine, phenobarbital, phenytoin, theophylline, and valproic acid to human serum alpha-1 acid glycoprotein (orosomucoid) and to human serum albumin separately in vitro was investigated using equilibrium dialysis of the unlabeled drugs. Each drug was studied at a therapeutic concentration. Alpha-1 acid glycoprotein was studied at one elevated and two physiological concentrations, whereas albumin was studied at one physiological and two low concentrations.

The effect of parenteral nutrition fluids on the binding of therapeutic drugs to human serum in vitro.

The competitive binding of seven therapeutic drugs (carbamazepine, phenytoin, phenobarbital, procainamide, quinidine, theophylline, and valproic acid) to human serum and to five commonly used parenteral nutrition fluids in vitro was studied using equilibrium dialysis. For five of the drugs, all parenteral nutrition fluids bound less drug than human serum-phenobarbital (up to 14% less), phenytoin (up to 46% less), procainamide (up to 43% less), quinidine (up to 25% less), and valproic acid (up to 77% less)-suggesting that the presence of these fluids might increase the free fraction of these drugs in vivo. For carbamazepine, the fluids bound up to 82% more drug, suggesting that the presence of these fluids might decrease the free fraction of this drug in vivo.

The effect of ethanol and pH on the adsorption of drugs from simulated gastric fluid onto activated charcoal.

The effect of ethanol and pH on the adsorption of acetaminophen (ACET), phenobarbital (PHB), phenytoin (PHY), salicylic acid (SA), and theophylline (THEO) from simulated gastric fluid onto activated charcoal was studied. For the ethanol study, each drug was prepared at a concentration of 10 g/L in ethanol; in hydrochloric acid (HCl), 1.2 mol/L; and in HCl, 1.

Procainamide and quinidine inhibition of the human hepatic degradation of meperidine in vitro.

Procainamide and quinidine inhibition of the degradation of meperidine in human liver was investigated by incubation of two concentrations of either drug with meperidine in homogenates of human liver over 24 and 36 h. Meperidine concentrations declined by 26% after incubation for 24 h and by 42% after incubation for 36 h. In the presence of procainamide, however, they decreased by only 15% to 18% at 24 h and by only 26% to 28% at 36 h.