Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity.

The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S═O, consistent with MsOH being crucial for high selectivity.

Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes.

A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-coupling product in high ee and good yield.

Pharmacodynamic interaction study of Allium sativum (garlic) with cilostazol in patients with type II diabetes mellitus.

Aim: Garlic is available as an over-the-counter herbal supplement and is known to have antiplatelet properties. Because of scarcity of clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we tried to evaluate the effects of coadministration of single and multiple doses of garlic and cilostazol on platelet aggregation.

Materials And Methods: The study was a randomized, open label, placebo-controlled, crossover study of type II diabetic patients, where 14 patients were enrolled and 10 completed the study.

Identification and characterization of potential impurities of donepezil.

Five unknown impurities ranging from 0.05 to 0.2% in donepezil were detected by a simple isocratic reversed-phase high performance liquid chromatography (HPLC).