Asymmetric ion-pairing catalysis.

Charged intermediates and reagents are ubiquitous in organic transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small molecules has emerged as a powerful strategy for catalytic, enantioselective synthesis. This review describes developments in the burgeoning field of asymmetric ion-pairing catalysis with an emphasis on the insights that have been gleaned into the structural and mechanistic features that contribute to high asymmetric induction.

Asymmetric Rh(I)-catalyzed addition of MIDA boronates to N-tert-butanesulfinyl aldimines: development and comparison to trifluoroborates.

The Rh(I)-catalyzed addition of alkenyl and aryl MIDA boronates to N-tert-butanesulfinyl aromatic and aliphatic imines proceeds in good yields (up to 99%) and with very high selectivity (98:2 to >99:1). In comparison to trifluoroborates, higher yields and selectivities are observed for the addition to N-tert-butanesulfinyl aromatic imines. This new method expands upon the versatility of the Rh(I)-catalyzed addition of boron reagents to imines, thereby further enabling the synthesis of chiral alpha-branched amines.

Total synthesis of (-)-aurantioclavine.

The concise total synthesis of (-)-aurantioclavine has been achieved by taking advantage of strategies for the asymmetric alkenylation of N-tert-butanesulfinyl imines. The enantiomerically pure natural product was prepared in 6 steps and 27% overall yield by using Rh-catalyzed addition of a N-methyliminodiacetic acid (MIDA) boronate and in 5 steps and 29% yield by employing a Grignard reagent addition sequence.

Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy.

A century after discovering that the Trypanosoma cruzi parasite is the etiological agent of Chagas disease, treatment is still plagued by limited efficacy, toxicity, and the emergence of drug resistance. The development of inhibitors of the major T. cruzi cysteine protease, cruzain, has been demonstrated to be a promising drug discovery avenue for this neglected disease.

General one-pot method for the preparation of N-tert-butanesulfinylamine diastereomer mixtures as standards for stereoselectivity determinations.

The one-pot preparation of N-sulfinylamine diastereomers proceeds in excellent yields (84-98%) for a diverse set of N-sulfinyl imine addition products. The method is operationally simple and extractive isolation provides analytically pure mixtures of diastereomers as standards for the rapid and accurate determination of N-sulfinylamine diastereomeric purity.

Asymmetric synthesis of alpha-branched allylic amines by the Rh(I)-catalyzed addition of alkenyltrifluoroborates to N-tert-butanesulfinyl aldimines.

The first Rh(I)-catalyzed addition of alkenylboron reagents to imines is described. The Rh(I)-catalyzed addition of potassium alkenyltrifluoroborate salts to both aromatic and aliphatic N-tert-butanesulfinyl aldimines proceeds in good yields (up to 97%) and with very high diastereoselectivities (95:5 to >99:1). This new method enables the general and efficient asymmetric synthesis of the important class of alpha-branched allylic amines from readily available and stable starting materials.

Identification of a new class of nonpeptidic inhibitors of cruzain.

Cruzain is the major cysteine protease of Trypanosoma cruzi, which is the causative agent of Chagas disease and is a promising target for the development of new chemotherapy. With the goal of developing potent nonpeptidic inhibitors of cruzain, the substrate activity screening (SAS) method was used to screen a library of protease substrates initially designed to target the homologous human protease cathepsin S. Structure-based design was next used to further improve substrate cleavage efficiency by introducing additional binding interactions in the S3 pocket of cruzain.

Comparative study of the effects of electrical stimulation in the nucleus accumbens, the mediodorsal thalamic nucleus and the bed nucleus of the stria terminalis in rats with schedule-induced polydipsia.

In the schedule-induced polydipsia model, hungry rats receiving a food pellet every minute will display excessive drinking behaviour (compulsive behaviour). We aimed 1) to evaluate if electrical stimulation in the nucleus accumbens (N ACC), the mediodorsal thalamic nucleus (MD) or the bed nucleus of the stria terminalis (BST) can decrease water intake in the schedule-induced polydipsia model; 2) to compare water intake between these groups for different stimulation amplitudes; and 3) to compare the effect of low frequency (2 Hz) with high frequency (100 Hz) stimulation. Rats were randomly divided into four groups: electrode implanted in the 1) N ACC (n=7), 2) MD (n=8), 3) BST (n=8), or 4) a sham-operated control group (n=7).