Concise route to a series of novel 3-(tetrazol-5-yl)quinoxalin-2(1H)-ones

This report presents a novel three step solution phase protocol to synthesize 3-(tetrazol-5-yl)quinoxalin-2(1H)-ones. The strategy utilizes ethyl glyoxalate and mono-N-Boc-protected-o-phenylenediamine derivatives in the Ugi-Azide multi-component reaction (MCR) to generate a unique 1,5-disubstituted tetrazole. Subsequent acid treatment stimulates a simultaneous Boc deprotection and intramolecular cyclization leading to bis-3,4-dihydroquinoxalinone tetrazoles. Direct oxidation using a stable solid-phase radical catalyst (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) with ceric ammonium nitrate (CAN) in catalytic fashion initiating aerobic oxidation, completes the entire procedure to generate a series of original unique bis-quinoxalinone tetrazoles. The method was also expanded to produce a bis-benzodiazepine tetrazole.     

An alternative synthesis of the lipophilic tail portion of abediterol using linear-selective hydroformylation

Abediterol is a compound currently in development for the treatment of respiratory disease at AstraZeneca. In this work we employ hydroformylation, an under-utilised reaction in the synthesis of pharmaceutical intermediates, as a key step to access the lipophilic amine portion of this molecule. The route described herein addresses some of the issues identified in the original route. Namely, hazardous materials are avoided and increased levels of control – from a process chemistry point of view – are demonstrated, with isolation of intermediates possible at multiple points in the synthesis. This work provides ‘proof-of-concept’ for an alternative synthetic route and provides high-quality material using a series of robust transformations.     

Flow-aligning and tumbling in small-molecule liquid crystals: pure components and mixtures

The results of an experimental study to measure the tumbling parameter, λ, for various small-molecule liquid crystals and their mixtures are presented. The methods used include textural observations (twist walls), a direct method, a rheological method, and the oscillatory method developed by Mather, Pearson, and Burghardt in 1995. The single-component results are compared with a molecular theory derived in 1995 by Archer and Larson as well as Kröger and Sellers, which predicts the temperature dependence of λ, while the results from the binary mixtures are compared to a continuum theory derived by Rey in 1996, giving the concentration dependence of λ. The results from the four experimental methods agree with each other for single-component liquid crystals, but not for mixtures. This suggests a failure of the single director Leslie-Ericksen theory to describe the rheology of liquid crystal mixtures.     

On the Decomposition of Order-Separable Posets of Countable Width into Chains

Order - A partially ordered set X has countable width if and only if every collection of pairwise incomparable elements of X is countable. It is order-separable if and only if there is a countable...     

Relative Asymmetric Induction in Formation of Substituted Cyclopentanols Via Intramolecular Carjbonyl Additions

Relative asymmetric induction in intramolecular carbonyl addition reactions has been studied for the first time in a systematic fashion. An empirical model has been proposed to rationalize the results.     

A non‐natural dinucleotide containing an isomeric l‐related deoxy­nucleoside: dinucleotide inhibitors of anti‐HIV integrase activity

The first X‐ray crystal structure of a non‐natural dinucleotide, 5′‐O‐phosphoryl‐1′‐deoxy‐2′‐isoadenylyl‐(3′ → 5′)‐cytidine 6.5‐hydrate (pIsodApC), C₁₉H₂₆N₈O₁₃P₂·6.5H₂O, belonging to a family of dinucleotides that contain an isomeric nucleoside component, is described. A complex system of hydrogen bonds between water mol­ecules and various sites on the dinucleotide was found. All H atoms were located from electron‐density difference maps, which allowed identification of protonation sites. Compounds of this family have been found to bind at the active site of HIV integrase and to be inhibitors of this key viral enzyme. These dinucleotides are completely resistant to cleavage by exonucleases; an abnormal dihedral angle twist in an inter­nucleotide phosphate bond revealed in the X‐ray crystal structure may be contributing to this unusual stability towards nucleases.     

Terrein

The fungal metabolite terrein (alternative name: trans‐2,3‐di­hydroxy‐4‐propenyl­cyclo­pent‐4‐enone), C₈H₁₀O₃, forms monoclinic (P2₁) crystals. The mol­ecules form hydrogen‐bonded chains, with O?O distances of 2.7115 (16) and 2.8155 (15) Å.     

Simultaneous Determination of Carvedilol,Enalaprilat, and Perindoprilat in Human Plasma Using LC–MS/MS and Its Application to a Pharmacokinetic Pilot Study

Chromatographia - A method for the extraction and quantification of carvedilol, enalaprilat, and perindoprilat in 50 µL human plasma, using high-performance liquid chromatography with...