ABSTRACT
Treatment of peracetylated alkyl and aryl 1,2-trans-glycosides with iodine in the presence of HMDS has been found to result in the anomerization leading to the formation of the respective 1,2-cis-glycosides. In the case of alkyl glycosides with aglycons of short alkyl chain length complete anomerization to the alpha-glycosides was observed while with those of longer chain length the process was found to be incomplete. The observations have been interpreted mechanistically.
Subject(s)
Glycosides/chemistry , Iodine/chemistry , Silanes/chemistry , Acetylation , Indicators and Reagents/chemistry , Oxygen/chemistry , StereoisomerismABSTRACT
A simple, mild, and regioselective method has been developed for the selective benzylation and p-methoxybenzylation of carbohydrate derivatives in high yields using Ag(2)CO(3) as the promoter. Benzylation of base-labile substrates, for which other reported methods are of little use, has been performed in high yields.
Subject(s)
Benzene Derivatives/chemistry , Carbohydrates/chemistry , Carbonates/pharmacology , Silver Compounds/pharmacology , Catalysis , Models, Chemical , Molecular Structure , StereoisomerismABSTRACT
A study was carried out to investigate compatibility of atenolol, a beta(1) blocker, with a variety of pharmaceutical excipients. The binary mixtures (1:1) of atenolol with the excipients were stored for 1 month at 40 degrees C/75% RH. The samples were directly observed for the physical changes, and also analyzed by a validated HPLC method to determine the chemical changes. The study revealed that atenolol was incompatible with ascorbic acid, citric acid and butylated hydroxyanisole. The degradation/interaction products formed in these mixtures were characterized by high resolution mass spectrometric and fragmentation analyses, using a LC-MS/TOF system. The identity of characterized structures was justified through mechanistic explanations.
Subject(s)
Adrenergic beta-Antagonists/chemistry , Atenolol/chemistry , Ascorbic Acid/chemistry , Butylated Hydroxyanisole , Chromatography, High Pressure Liquid , Citric Acid/chemistry , Drug Incompatibility , Excipients/chemistry , Hydrogen-Ion Concentration , Indicators and Reagents , Mass Spectrometry , Pharmaceutic Aids , Spectrophotometry, UltravioletABSTRACT
A polypill for cardiovascular diseases (CVD) is under development. It is proposed to contain a combination of antithrombotic agent (aspirin), low-dose blood pressure lowering agents, i.e., angiotensin-converting enzyme inhibitor (lisinopril), one among a beta-blocker (atenolol) or diuretic (hydrochlorothiazide), and a statin (simvastatin/atorvastatin/pravatsatin, etc.). Due to the presence of multiple drugs in the same formulation, there is a strong likelihood of interaction among the drugs and/or their products. In a previous study, we observed formation of a number of interaction/degradation products from atenolol and lisinopril in the presence of aspirin. Accordingly, the purpose of this study was to characterize the resolved products using high resolution mass spectrometric and fragmentation analyses using a LC-MS/TOF system. Initially, studies were carried out on the drugs (atenolol, lisinopril and aspirin) to establish their complete fragmentation pattern. These studies were then extended to degraded samples to postulate the structures of interaction/degradation products. The characterized structures were justified through mechanistic explanations.
