Mladen Vinkovic

Conformational analysis of azithromycin by nuclear magnetic resonance spectroscopy and molecular modelling

Abstract The conformation of azithromycin 1 in the solution was determined by NMR spectroscopy and molecular mechanics calculations and compared with its crystal structure and with some erythromycin derivatives. In solution 1 exists predominantly in a “folded-in” conformation in the C-3 to C-5 region, whereas its crystal state conformation is “folded-out”.

Conformational analysis of 9-deoxo-9a-aza-9a- and 9-deoxo-8a-aza-8a-homoerythromycin A 6,9-cyclic iminoethers

Abstract The conformation of 9a- 4 and 8a- 5 bicyclic iminoethers, the key synthetic intermediates of 15-membered AZALIDES was determined. The 2D NMR data and molecular modeling techniques were used to establish the predominant solution-state conformation. Conformational analysis suggests that in reduction of the iminoethers the smaller ring in both bicyclic compounds, as well as steric effects around the imidate group are reactivity-determined factors. The invariance in coupling constants indicates that 4 and 5 do not change conformation, when they go from a polar to a hydrophobic environment.

Acyclic Purine Nucleoside Analogues - Computational and NMR Studies of Conformational Behaviour

Abstract The conformational space of N -7- and N -9-(2-hydroxypropyl)-6-( N -pyrrolyl)purine as well as of N -7- and N -9-(2,3-dihydroxypropyl)-6-( N -pyrrolyl)purine has been studied by molecular mechanics (MMX force field) and semiempirical (PM3) calculations. Eight local minima were obtained for the N -7-(2-hydroxypropyl) regioisomer by the MMX force field and reoptimised by the PM3 method to locate the global minimum. The conformation of the N -7-(2,3-dihydroxypropyl) regioisomer is locked by intramolecular H-bonding and therefore more rigid. The results of theoretical calculations are in agreement with 1 H and 13 C NMR analysis of substituent chemical shifts, Cue5f8H and Hue5f8H coupling constants and connectivities in 2D homo- and heteronuclear correlation spectra.

Two novel optically active penam derivatives

The X-ray structure analyses of the two optically active penam derivatives, (2S,4S,5R,6S)-2-benzylcarbamoyl-6-bromo-3,3-dimethyl-4-thia-1-azabicyclo[3.2.0]heptan-7-one 4-oxide hydrate, C 15 H 17 BrN 2 O 3 S.H 2 O, (I), and (5R)-3-benzylimino-2-isopropylidene-4-thia-1-azabicyclo[3.2.0]heptan-7-one, C 15 H 16 N 2 OS, (II), have been determined in order to ascertain their absolute configurations. Both compounds adopt the open-book conformation for the fused β-lactam and thiazolidine rings. The β-lactam ring is in a distorted planar conformation, while the thiazolidine ring is in an envelope conformation. The pyramidalization effect of the N1 atom in both compounds has been characterized by a displacement of the N atom from the plane of its substituents: the N atom is displaced 0.344 (5) and 0.350 (5) A in molecules A and B of compound (I) and 0.410 (5) A in compound (II).

Functional derivatives of 4-oxoazetidine-2-sulfinic acids in asymmetric synthesis of 2-azacepham sulfoxides and their transformation

Abstract The enantiomerically pure 2-azacepham sulfoxide 2a was synthesized by stereocontrolled intramolecular cyclization of sulfinates 3 or sulfinamides 8 in the presence of dry hydrogen chloride followed by triethylamine. The cyclization accrued via equilibrated mixtures of sulfinyl chlorides 10a 10b , which presence was confirmed by chemical transformations. The absolute configuration of the sulfinic acid 9a as a product of their hydrolysis was determinate by a single crystal X-ray analysis.