Unprecedented Epimerization of an Azithromycin Analogue: Synthesis,Structure and Biological Activity of 2′-Dehydroxy-5″-Epi-Azithromycin

Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton–McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.     

Synthesis of aliphatic polyesters by controlled ring-opening polymerization of cyclic esters. Characterization,properties, transesterification reactions

The polymerization of (D,L)-Lactide at room temperature in solution using Y(OCH₂CH₂OiPr)₃ and Ln₅(μ-O)(OiPr)₁₃ with Ln = La, Sm, Y, Yb as initiators was studied. According to kinetic data, a controlled type polymerization is observed for most of the systems. La μ-oxoisopropoxide is the most reactive initiator, but leads to a substantial broadening of molecular weight distribution at high conversions. The nature of transesterification reactions was studied by SEC, ¹³C NMR and MALDI-TOF MS techniques. For Sm and Y-μ-oxo initiators only limited intermolecular ester exchange occurs, while with La μ-oxoinitiator and with Y(OCH₂CH₂OiPr)₃ initiator, but after a long time of the polymerization reaction, both inter and intramolecular transesterification occur with formation of cyclics.     

Stereochemical aspects of the controlled ring-opening polymerization of chiral cyclic esters

The stereochemical aspects of controlled polymerization of lactide and β-butyrolactone are discussed. The physicochemical and thermal properties of these polymers are shown to be depending on the stereochemical structure of the macromolecular chain. Different types of processes involving change of enantiomeric composition in the course of the polymerization reaction are examined in function of different initiators used. The formation of stereocomplexes from stereocopolymers of various enantiomeric compositions is reported.     

Creep relaxation and stress relaxation of PS-HI/SEBS blends

For the selection of the polymer materials and polymer blends for various fields of applications the stability of material under constant deformation and constant load are very important. In this paper, the copolymers high-impact polystyrene, PS-HI, styrene-ethylene/buthylene-styrene block copolymer, SEBS, and their blends PS-HI/SEBS were investigated. The investigations were done by DMA analysis. The secondary viscoelastic functions, creep, creep modulus, stress and flexural relaxation modulus were investigated in creep and stress relaxation experiment at temperatures 25, 35, 45, 55 and 65°C during 1 h. The master curves were created by time-temperature correspondence principle, TTC. The correlation of the secondary viscoelastic functions with time, temperature and content of the hard, PS, phase was discussed.     

The control of morphology and structure of galvanostatically produced tin dendrites by analysis of chronopotentiometry response

Journal of Solid State Electrochemistry - The influence of chronopotentiometry response on the morphology and structure of galvanostatically synthesized tin dendritic particles has been...