Synthesis of potential biologically active derivatives of beta-cyclodextrins.

摘要

Cyclodextrins, the cyclic oligosaccharides containing several primary and secondary hydroxyl groups, can be selectively modified to create derivatives that function as artificial enzymes, drug delivery systems and chiral separation media. Superior binding ability and solubility of these derivatives compared to pure Cyclodextrins make them desirable in pharmaceutical industry. Investigation described in this dissertation consists of two modified cyclodextrin systems, one in which a flavin molecule (flaovcyclodextrin system) and the other in which a porphyrin molecule (porphyrinocyclodextrin system) is covalently attached to cyclodextrin.; Although flavo-enzymes are very important natural redox enzymes, which catalyze a variety of biological reactions, they are not stable under non-biological conditions. Artificial enzymes that can function under non-biological conditions can offer the functionality of a real enzyme without its instability. Flavo-cyclodextrin system is an artificial enzyme that has the potential to accelerate a variety of reactions such as oxidation, hydroxylation and dehydrogenation. These artificial enzymes are synthesized by first selectively modifying a hydroxyl group of cyclodextrin to attach the N-methylamino nitrobenzyl group. This is further reduced and condensed with alloxan monohydrate to obtain the desired flavo-cyclodextrin.; Porphyrins and expanded porphyrins have been used as photodynamic therapy (PDT) agents. Since Cyclodextrins have been used in the pharmaceutical industry, attaching porphyrin systems to them is expected to significantly improve the characteristics of PDT agents. A new synthetic methodology, which involves building porphyrin on to cyclodextrin as opposed to attaching the porphyrin to the cyclodextrin through a linker, is developed and will be discussed in detail in this dissertation.