Marcos José Souza Carpes

Heck arylations of N-acyl-3-pyrroline and N-acyl-1,2,5,6-tetrahydropyridine with aryldiazonium salts. Short syntheses of aryl γ- and δ-lactams, baclofen, homobaclofen and analogues

Heck arylation of N-acyl-3-pyrrolines and an N-acyl-tetrahydropyridine with aryldiazonium tetrafluoroborates under phosphine-free conditions proceeded smoothly to give α-hydroxycarbamates (hemiaminals) or α-alkoxycarbamates which were oxidized to the desired γ- and δ-lactams. Acidic hydrolysis of the γ-lactams produced a series of arylated GABA derivatives, including baclofen, a useful therapeutic drug, in only three steps with an overall yield of 63–76%. Starting from N-acyl-tetrahydropyridine, aryl-δ-lactams and higher homologues of baclofen can be obtained.

CROMATOGRAFIA EM LEITO MÓVEL SIMULADO NA PRODUÇÃO DE SUBSTÂNCIAS ENANTIOMERICAMENTE PURAS OU ENRIQUECIDAS EM LARGA ESCALA

There is great interest nowadays in the use of preparative liquid chromatography as an effective tool for the production of enantiomerically pure, or enriched, compounds for the pharmaceutical industry. To make the chromatographic process economically attractive, attention is now focused on the choice of the chromatographic operating mode to minimize eluent consumption and to maximize productivity. Among the alternatives to the traditional batch chromatography, attention is now shifting towards simulated moving bed (SMB) technologies and a review covering the latest developments in this area seems timely. Several aspects of this important analytical technique are presented and details concerning the SMB technology for process optimization are outlined.

D, L-cis-2,3-Pyrrolidine dicarboxylate alters [3H]-L-glutamate binding and induces convulsions in mice

This study investigated whether D,L-cis-2,3-Pyrrolidine dicarboxylate (D,L-cis-2,3-PDC), a new glutamate analogue, alters glutamate binding to cerebral plasma membranes and whether N-methyl-D-aspartate (NMDA) receptors are involved in the convulsant effect of this compound. D,L-cis-2,3-PDC reduced sodium-independent [3H]-L-glutamate binding to lysed membrane preparations from adult rat cortex and had no effect on sodium-dependent glutamate binding. Intracerebroventricular administration of D,L-cis-2,3-PDC (7.5-25 nmol/5 microl) induced generalized tonic-clonic convulsions in mice in a dose-dependent manner. The coadministration of MK-801 (7 nmol/2.5 microl), with D,L-cis-2,3-PDC (16.5 nmol/2.5 microl), fully protected the animals against D,L-cis-2,3-PDC-induced convulsions, while the coadministration of DNQX (10 nmol/2.5 microl) increased the latency to convulsions but did not alter the percentage of animals that had convulsions. These results suggest that D,L-cis-2,3-PDC-induced effects are mediated predominantly by NMDA receptors.