Studi su macrociclizzazioni intramolecolari fotoindotte su eliche peptidiche-310

In this Thesis project three hexapeptides were synthesized, rich in the helicogenic Aib, and containing a Met and a Bpa residue. Bpa has been extensively used in recent studies as a probe in the investigation of ligand-receptor interactions [1]. The synthesis has been carried out by solution methods, with a step-by-step approach. Here are listed the three amino acid sequences: (1) Boc-Aib-Met-Aib-Aib-Bpa-Aib-OMe (i . i+3) (2) Boc-Aib-Bpa-Aib-Met-Aib-Aib-OMe (i . i+2) (3) Boc-Aib-Bpa-Met-Aib-Aib-Aib-OMe (i . i+1) Macroring formation can be exploited to obtain peptides with a more rigid conformation and to increase peptide stability to proteolytic attack. In our work, therefore, we investigated the intramolecular, photo-activated reaction between Bpa and Met leading to an annular system (Paternò-Yang photocyclization). We focused on the effect of increasing spacer length, (Aib)n, on the stereo- and regioselectivities of reaction and compared it to that reported in a previous study [2]. The FT/IR absorption and 1H-NMR conformational analyses indicate, as expected, a 3-10 helical folding for all hexapeptides. The photocyclization reaction was carried out by exposing the reagents to 16 monochromatic lamps irradiating at . = 350 nm for 60 minutes. Analysis on the products confirmed that the intramolecular reaction does occur, but with significant differences in terms of the products obtained. The most regioselective reaction (on the e-methyl function of the Met side chain) turned out to be that performed on sequence