Groussier, Marianne Françoise Andrée; (2000) A new orthogonal protecting group strategy for lanthionine-containing peptides. Doctoral thesis (Ph.D), UCL (University College London).

Text A_new_orthogonal_protecting_gr.pdf Download (8MB)

Abstract

The synthesis of lanthionine residues bearing photolabile protecting groups and the use of these compounds for the synthesis of lanthionine-containing peptides is described in this thesis. A new orthogonal approach has been developed towards bridged peptidomimetics such as sandostatin analogs. Several synthetic pathways were followed to synthesise these lanthionine residues and several types of photolabile groups were also tried. The final route involves the making of (R, R) lanthionine residues bearing NV and NVOC groups from (^-serine and (R, i?)-cyStine. The intermediates (i^)-cysteine and (7^)-3-iodoalanine were synthesised with the appropriate protecting groups. The iodoalanine intermediates were obtained in high yields as mixtures of rotamers. They were subsequently used to synthesise the final lanthionine residues following a high-yielding and fast route. The formation of small amounts of diastereoisomers was observed. These were easily separated from the final compounds. Photolabile cleavages studies of NV and NVOC groups were carried out and optimised in solution before SPPS. Finally, several attempts at synthesising a sandostatin analog were carried out on a resin, incorporating the lanthionine residues into cyclic octapeptides. Difficulties were encountered during photolabile cleavages on a polystyrene support. However, efficient photolabile cleavage was finally obtained on Tentagel resin. Other sections of this thesis describe the large family of lanthionine-containing peptide lantibiotics and synthetic routes leading to lanthionine residues as well as the different strategies elaborated for the cyclisation of small peptides.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item