Amir Avdagić

LC―NMR and LC―MS identification of an impurity in a novel antifungal drug icofungipen

Successful use of LC-NMR and LC-MS for rapid identification of an impurity in a novel antifungal drug icofungipen has been demonstrated. Complementary information obtained from the two methods made it possible to determine the structure of A1 prior to its isolation and purification. Stop-flow LC-NMR ((1)H and DQFCOSY), LC-MS and LC-MS/MS spectra have shown that A1 is structurally related to icofungipen. It was later isolated and prepared synthetically and its structure was corroborated by high-resolution NMR spectroscopy.

First example of the solvent effect on absolute conformation of chiral 3,3-disubstituted 1,4-benzodiazepin-2-ones

Abstract Chiral 3,3-disubstituted 1,4-benzodiazepin-2-ones (3S)- 7 and (3S)- 8 reveal solvent dependent conformational equilibria. The conformer with absolute P-conformation, with CH2X (X = p-tosyl, Cl) group in a pseudoaxial (ψa) position and CH2OAc group in a pseudoequatorial (ψe) position, prevails in nonpolar solvents, as shown by 1H-NMR and CD spectra. For (3S)- 7 only a small shift of the conformational equilibrium in a polar solvent (DMSO) is observed, whereas compound (3S)- 8 inverts to a prevailing M-conformer. The inversion barrier for M P equilibrium is estimated on the bases of TDNMR data. For compounds (3R)- 5 and (3S)- 7, 8 the relative stability of the M P conformers in the ground state is calculated by the MM2 method; comparison of these results with CD and 1H-NMR data reveal that nonpolar solvents invert the relative stability calculated for the two conformers.

Long-distance control in stereoselective reduction of 3-[3-(4′-bromo[1,1′-biphenyl]-4-yl)-3-keto-1-phenylpropyl]-4-hydroxy-2H-1-benzopyran-2-one: Relative configuration of prevailing diastereomer and absolute configuration of its enantiomers

Depending on the reducing agent and reaction conditions, diastereoselective reduction of 3-[3-(4′-bromo[1,1′-biphenyl]-4-yl)-3-keto-1-phenylpropyl]-4-hydroxy-2H-1-benzopyran-2-one (2) proceeds with different stereoselectivity; a surprisingly high, approximately 90% d.e. of 4A is achieved with NaBH4 in MeOH at low temperature. Resulting diastereomeric racemates 4A and 4B are separated and their respective syn and anti configurations are assigned on the bases of mechanic considerations, supported by the 1H-NMR spectra and conformational analysis based on MM2 calculations. The syn diastereomer 7A, 4-OMe derivative of 4A, was partially resolved by acylation at C(3)-OH with S-(−)-camphanic acid to camphanyl ester 12 of (−)-7A, leaving (+)-enantiomer 7A. The assignment of absolute 1R,3S-configuration to (−)-7A is based on comparison of its CD spectrum with those of the model compounds S-14 and R-15, which represent partial chromophores 4-hydroxy-2H-1-benzopyran-2-one (4-hydroxycoumarin) A, and 4′-bromo-1,1′-biphenyl B; their exciton coupling in (−)-7A is suggested. Chirality 9:512–522, 1997.