فهرست مطالب sedigheh rezaeianpour

The basic chemical structure of most prostate specific membrane antigen (PSMA) inhibitors which are now in pre-clinical and clinical studies is Glu-Ureido-based peptides. Synthesis of urea-based PSMA inhibitors includes two steps: 1- isocyanate intermediate formation and 2- urea bond formation. In current methods, isocyanate is formed in liquid phase and then reacts with amine existing in liquid phase or bound to solid phase for urea bond formation. In this study, we developed a new facile method for formation of both isocyanate and urea on solid phase under standard peptide coupling conditions. The solid phase-bound isocyanate served as intermediate to form urea bond. To monitor reaction progress qualitative test (Kaiser Test) and On-Bead FT-IR spectroscopy were used. The structure of Glutamate-Urea-Lysine (EUK) was confirmed using LC-Mass and 1H-NMR. This novel method successfully applied to synthesize of another urea-based peptide containing a sequence of Glu-Urea-Lys(OMe)-GABA-Tyr-Tyr-GABA and the bifunctional linker hydrazinonicotinamide (HYNIC) as well.

Equatorial/axial conversion in piperidine and phosphorinane with different substituents wereinvestigated with great details. Three possible routes, i.e. heteroatom inversion and two ring inversiontype were considered. Ring conversion can occur via two pathways one starts with ring flatteningfrom the heteroatom site (nitrogen in piperidine and phosphorous in phosphorinane) and the otherinitiates by ring flattening in the C4 position, facing the nitrogen/ phosphorous site. Densityfunctional theory calculations are applied at B3LYP/6-311+G(d,p)// B3LYP/6-31G(d) level. Thefeasibility of equatorial/axial conversion for the substituted piperidine rings was found to be in theorder of H>CH3>Cl~OH~F, whereas for phosphorinane it turns out to be as F>OH>Cl~ H~CH3. Inthe piperidine derivatives hydrogen and methyl substituents the atom inversion route is dominantprocess while the other substituents (Cl, F, OH) one of the two possible ring inversion is favored. Forthe phosphorinane, however, ring inversion is the favored route for all substituents.