HETEROCYCLICAL COMPOUNDS (3)

Author: MONTAÑEZ VEGA MARÍA ISABEL.
Year: 2006.
University: MÁLAGA [www.uma.es].
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS, UNIVERSIDAD DE MÁLAGA.

Summary: In clinical practice the use of the kits currently marketed by pharmaceutical companies for the diagnosis of allergy to beta-lactámicos presents some controversy, which has carried out a very detailed study of this topic. Following evaluation of the stability of aqueous solutions of bencilpeniciloato sodium (2) and amoxiciloato sodium (5), it appears that this product hydrolysis ring beta-lactama of penicillins, epimeriza readily in aqueous solution. The epimerización takes place exclusively by recemecización of C-5 of thiazolidine ring and only via an intermediate type imina. Products aminolisis (6) and (7), on the other hand, have a comparatively greater stability. We carried out the synthesis of structures type 31 that, according to our hypothesis, could prove dela conjugation of cephalosporins, These products CH3 in the carbon that was originally in position 6 of the cephalosporin (Z-38, 39, 40, 41, 42 and 43) were specifically recognized by IgE antibodies in patients who have presented an episode allergic to the corresponding cephalosporins with the same side chain R1. The funcionalización this additional carbon (CH2OH) (Z-53, 56, 58, 60, 62 and 64), seems to imply an improvement in the recognition IgE, while the study of the corresponding derivative with a thiol group (CH2SH) (Z-77, 79, 72, 84, 87 and 89) has not led to improvements in the recognition process. The composite rate 31 incorporates appropriate that the epitope recognized by IgE antibodies, and the functional group at C-3 could modulate the level of recognition. The use of dendrímeros type poliamidoamina, PAMAM of different generations (0-6) allowed prepare antigens dendriméricos synthetic funcionalizados on its surface with groups bencilpeniciloilo BPO, structures and arrangements with well-defined space from the chemical point of view. These new compounds are recognized by IgE so the dendrímeros PAMAM emulate adequately to the natural protein responsible for the formation of conjugated in vivo. It has also successfully tackled the preparation of equivalents derived antigéncios dendriméricos amoxicillin. The dendrímeros PAMAN were supported on solid phases type cellulose and funcionalizados with antigenic determinants to beta-lactama (type BPO), to form antigens dendriméricos synthetic incurred in solid phase, appropriate methods to be applied to the qualification of IgE antibodies type RAST. The binding of dendriméricos synthetic incurred in solid phase, appropriate to be applied to methods of measuring IgE antibodies type RAST. The binding of dendrímero to the solid phase was carried out through 4 different procedures activation of hydroxyl from cellulose as: A-BrCN B-Alfa-halohaluros of alcanoílo. C-Haluros of alcanoílo presenting chain space. D-Trimetilaminopropilsilano TMAPS. It has been possible to assess and quantify the number of structures dendriméricas antigenic and the number of BPO units, which are supported on the solid phase. The process of molecular recognition by the IGE to antigens dendriméricos synthetic supported on the solid phase can be facilitated if between the solid phase and the derivative dendrimérico connects a spacer type polietilengolicol. Early studies of IgE determination by RAST indicate a greater willingness of the antigens dendirméricos synthetic supported on this solid phase as compared with other methods used in this report.