Supervisors info:
Δημήτρης Γεωργιάδης, Αναπληρωτής Καθηγητής, τμήμα Χημείας, ΕΚΠΑ
Summary:
The synthesis phosphinic peptides, a class of metalloenzyme inhibitors that act as transition state analogues, is a highly important target since optimization of their biological activity relies heavily on specific structural requirements. The development of reliable synthetic protocols for the preparation lack of core phosphinic pseudodipeptidic units renders a key point of inquiry. At this thesis, we have developed an orthogonal synthetic protocol that enables the preparation of suitably protected building blocks for solid-phase peptide synthesis. It was found that by using a suitable protecting group, maximum orthogonality is achieved among the protecting groups of the phosphinic, amine and carboxylic termini, as well as the protecting groups of the side chains. A new and improved protocol of Fmoc-protected phosphinic units, suitably protected for the requirements of SPPS, which can be applied in cases of sensitive funvtional and protecting groups. Subsequently, the adamantylation reaction and deprotection of the carboxy terminus reaction are optimized. Finally, aminophosphinic units that are inaccessible by following current methologies were synthesized, proving the wide scope and supremacy of the described protocol.
Keywords:
Organic Synthesis, Orthogonality, Protective groups, P-Michael, Phosphinic Acid
