Evaluation of the Macrocyclic Antibiotic Avoparcin as a New Chiral Selector for HPLC

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

Detection of amino acids and their enantiomeric ratios in various samples, and the development of a new stationary phase for the chiral separation of amino acids

“The study of amino acids is very important in the food industry, pharmaceutical industry, and the medical field. Over the past twenty years, studies have found higher than expected levels of D-amino acids in foods and beverages. Despite the fact that several studies have reported the concentrations of various free amino acids in tobacco, their enantiomeric composition is unknown. Both the absolute and enantiomeric compositions of proline, alanine, asparagine, aspartic acid, valine, methionine, leucine, and phenylalanine were determined for three strains of tobacco leaf, three types of smokeless tobacco, and six different blended filtered and non-filtered reference cigarettes. Some of the highest levels of D-amino acids ever found in agricultural products were observed. Possible mechanisms for the production of these D-amino acids are considered. The relevance of D-amino acids in tobacco is discussed. Many chiral thiols such as cysteine, homocysteine, N-acetylcysteine (NAC), and penicillamine are biologically important compounds. Among other roles, they act as antioxidants, therapeutic agents, and indicators of disease. Like other amino acids in biological samples, they are usually derivatized to enhance sensitivity in detection. But most derivatizing agents react with the amine group. Selectively derivatizing only the thiol moiety with a fluorescent group eliminates the large number of amine containing background compounds that are present in biological samples. Most of these thiol specific derivatizing agents require complex and lengthy reactions and produce unstable derivatives. And there have been few reports on the enantiomeric resolution of thiol containing amino acids which have been fluorescently tagged exclusively through the sulfhydryl group. The first HPLC enantioresolution of N(l-pyrenyl)maleimide (NPM) and ThioGlo™3 derivatized compounds is reported on teicoplanin and naphthylethyl- carbamate-ß-cylclodextrin (NEC-P-CD) chiral stationary phases. Macrocyclic antibiotics have proven to be very selective and widely applicable chiral stationary phases (CSPs). The teicoplanin CSP has produced some of the best separations for amino acids as well as other types of compounds. Two similar CSPs are produced and compared to the teicoplanin CSP. The first is an aglycone of teicoplanin produced by removing the three carbohydrate moieties from tiecoplanin. This CSP proved to be highly selective for amino acids and provided insight into the role of these sugar units for the antibiotic. The second CSP is made from another macrocyclic antibiotic, A-40,926 which is structurally very similar to teicoplanin. This CSP did not prove to be superior to the teicoplanin CSP for any specific class of compounds, but did prove to be more retentive and provide higher resolution for many compounds”--Abstract, page iv

Resolution of Chiral Thiol Compounds Derivatized with N-(1-pyrenyl)-maleimide and Thioglo™3

Many chiral thiols such as cysteine, homocysteine, N-acetylcysteine (NAC), and penicillamine are biologically important compounds. Among other roles, they act as antioxidants, therapeutic agents and indicators of disease. when analyzing low levels of these compounds, they are often derivatized in order to increase the sensitivity of the determination. However, it is generally an associated amine functional group that is derivatized. by selectively derivatizing only the thiol moiety with a fluorescent group, one is able to eliminate the large number of amine containing background compounds that are present in biological samples. However, there have been few reports on the enantiomeric resolution of thiol containing amino acids in which the fluorescent tag is linked exclusively through the sulfhydryl group. The first HPLC enantioresolution of N(1-pyrenyl)maleimide (NPM) and ThioGlo™3 derivatized compounds is reported on Teicoplanin and naphthylethyl-carbamate-β-cyclodextrin (NEC-β-CD) chiral stationary phases

Evaluation of the macrocyclic glycopeptide A-40,926 as a high-performance liquid chromatographic chiral selector and comparison with teicoplanin chiral stationary phase

A new macrocyclic antibiotic of the vancomycin family, referred to by its industrial designation as A-40,926, was bonded to 5 um silica particles and utilised as a chiral stationary phase (CSP). Since A-40,926 is structurally related to teicoplanin, the A-40,926 CSP was compared to a commercially available teicoplanin CSP. A set of 28 chiral compounds, including amino acids and related compounds, compounds with a ring containing the stereogenic centre, compounds bearing aromatic structures near their stereogenic centres and alcohols, was tested for enantioseparation on the two CSPs. The results are compared and discussed in terms of enantioselective Gibbs energy difference. The A-40,926 CSP was able to resolve one compound that was not resolved by the teicoplanin CSP. However, it could not separate four compounds that the teicoplanin CSP did separate. It is shown that the A-40,926 CSP is complementary to the teicoplanin CSP, thereby enlarging the number of enantiomers that can be separated by the macrocyclic glycopeptide based CSPs

Improved hepatic lipid composition following short-term exercise in nonalcoholic fatty liver disease

CONTEXT: Hepatic steatosis, insulin resistance, inflammation, low levels of polyunsaturated lipids, and adiponectin are implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We examined the effects of short-term aerobic exercise on these metabolic risk factors. DESIGN AND PARTICIPANTS: Obese individuals (N = 17, 34.3 ± 1.0 kg/m(2)) with clinically confirmed NAFLD were enrolled in a short-term aerobic exercise program that consisted of 7 consecutive days of treadmill walking at ∼85% of maximal heart rate for 60 minutes per day. Preintervention and postintervention measures included hepatic triglyceride content, and a lipid saturation index and polyunsaturated lipid index (PUI) of the liver, obtained by (1)H magnetic resonance spectroscopy (N = 14). Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT), and mononuclear cells were isolated to assess reactive oxygen species production during the OGTT. Circulating glucose, insulin, and high molecular weight (HMW) adiponectin were determined from plasma. MAIN OUTCOME: Short-term aerobic exercise training improved hepatic lipid composition in patients with NAFLD. RESULTS: Exercise training resulted in an increase in liver PUI (P < .05), increased insulin sensitivity (Matsuda Index: P < .05), HMW adiponectin (P < .05), and maximal oxygen consumption (P < .05). Reactive oxygen species production during the OGTT was reduced following exercise training (P < .05). HMW adiponectin was increased after the exercise program and the increase was positively correlated with the increase in liver PUI (r = 0.52, P = .05). Body weight remained stable during the program (P > .05). CONCLUSION: Short-term exercise can target hepatic lipid composition, which may reduce the risk of NAFLD progression. The improvement in hepatic lipid composition may be driven by adiponectin