Mixtures of randomly substituted sulfated cyclodextrins (degree of substitution, approximately 7-10) were successfully used as chiral additives for the enantioseparation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antihypertensives, antimalarials, relaxants, and bronchodilators. The separations were accomplished at pH 3.8, with the anode at the detector end of the column. Under these conditions, in which electroosmotic flow is directed toward the injection end of the column and the electrophoretic mobility of the negatively charged cyclodextrin is toward the detector, none of the analytes reached the detector in the absence of the sulfated cyclodextrin. Most (40) of the successfully resolved enantiomers contained basic functionality and a stereogenic carbon. However, the versatility of this sulfated cyclodextrin additive was also demonstrated by the fact that three atropisomers, 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate, 1.1'-binaphthyl-2,2'-diol, and Troger's base, and several neutral analytes were also successfully enantioresolved under these conditions. The separation mechanism seems to involve inclusion complexation.

Avoparcin is a macrocyclic glycopeptide antibiotic structurally related to vancomycin, teicoplanin, and ristocetin A. When attached to 5‐μm spherical silica gel, the avoparcin proved to be an effective chiral stationary phase (CSP) that could be used in the reversed‐phase, normal‐phase, and polar‐organic modes. The avoparcin CSP was complimentary to the other macrocyclic glycopeptide CSPs in that it could resolve some racemates that the others could not, and vice versa. Some important compounds resolved on the avoparcin CSP include verapamil, thyroxine, mephenytoin, and 2‐imidazolidone‐4‐carboxylic acid. The use of this CSP and the optimization of separations on it are discussed. Avoparcin appears to be a useful addition to this family of CSPs. Chirality 10:627–660, 1998. © 1998 Wiley‐Liss, Inc.

Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11beta-HSD1 inhibitors. However, the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer. A methyl group was added to the C-5 position to eliminate epimerization, leading to the discovery of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). This compound decreased fed blood glucose and insulin levels and reduced body weight in diet-induced obesity mice.

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