Investigation of functionalized α-chloroalkyllithiums for a stereospecific reagent-controlled homologation approach to the analgesic alkaloid (-)-epibatidine.

Four putative functionalized α-chloroakyllithiums RCH2CHLiCl, where R=CHCH2(18 a), CCH (18 b), CH2OBn (18 c), and CH[O(CH2)2O] (18 d), were generated in situ by sulfoxide-lithium exchange from α-chlorosulfoxides, and investigated for the stereospecific reagent-controlled homologation (StReCH) of phenethyl and 2-chloropyrid-5-yl (17) pinacol boronic esters. Deuterium labeling experiments revealed that α-chloroalkyllithiums are quenched by proton transfer from their α-chlorosulfoxide precursors and it was established that this effect compromises the yield of StReCH reactions. Use of α-deuterated α-chlorosulfoxides was discovered to ameliorate the problem by retarding the rate of acid-base chemistry between the carbenoid and its precursor.

Iterative stereospecific reagent-controlled homologation using a functionalized α-chloroalkyllithium: synthesis of cyclic targets related to epibatidine.

Enantioenriched 1-chloro-2-(1,3-dioxolan-2-yl)ethyllithium was generated by PhLi initiated sulfoxide-ligand exchange and deployed in situ for sequential double stereospecific reagent-controlled homologation (StReCH) of B-(2-chloro-pyrid-5-yl) pinacol boronate. This process afforded highly functionalized contiguous stereodiad motifs (typically, % ee ≥ 98%, dr ≥ 85:15) amenable to subsequent annulative transformations as demonstrated by the concise synthesis (5-7 steps) of cyclic adducts related to the analgesic alkaloid epibatidine.

Dexlansoprazole: A proton pump inhibitor with a dual delayed-release system.

Background: Dexlansoprazole, the dextrorotatory enantiomer of lansoprazole, is a proton pump inhibitor (PPI) formulated to have dual delayed-release properties. It is indicated for healing all grades of esophagitis, maintaining the healing of erosive esophagitis (EE), and treating heartburn associated with nonerosive gastroesophageal reflux disease.

Objective: This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of dexlansoprazole, as well as its clinical efficacy and tolerability.

Spontaneous symmetry breaking during interrupted crystallization of an axially chiral amino acid derivative.

High net enantiomeric excess was observed for crystal collections obtained by crystallization of the TFA salt of a configurationally stable yet racemic axially chiral amidoamine in EtOH solution with or without stirring (up to >99% ee at < or = 15% crystallization).

Rivaroxaban: a novel, oral, direct factor Xa inhibitor.

Thromboembolic disorders such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke often result in long-term disability and/or mortality. The anticoagulants currently available have been effective in the treatment and prevention of these disorders; however, parenteral administration, variable pharmacokinetics and pharmacodynamics, drug and dietary interactions, and a requirement for frequent monitoring of efficacy and safety limit use of these drugs. Rivaroxaban is a novel, oral factor Xa inhibitor in clinical development for the treatment and prevention of thromboembolic diseases.