| Abstract |
The subject of this study was the synthesis of optically pure γ-amino acids and di- and tetra-amines. The γ-amino acids exhibit biological activity either on their own or as components of more complicated molecules. γ-Amino butyric acid (GABA), the most widely studied γ-amino acid, is a neurotransmitter and the synthesis of its analogs is the starting point for the development of new medicinal agents. In chapter one, there is a report of the on the literature on the synthesis of γ-amino acids (α-, β-, γ-substituted), hydroxy-γ-amino acids and α,β-unsaturated γ-amino acids. In chapter two, the studies on the conformations of γ-peptides, are summarized. γ-Peptides show stable conformations either in polar or non polar environment, even if they contain four monomers, something that is not observed in α-amino acid peptides. This discovery is a pathfinder for the synthesis of non-hydrolyzable peptides and proteins that will have improved biological activity. In chapter three, there is a short report on δ-amino acids, compounds which can be prepared by similar synthetic routes as γ-amino acids. The synthesis of protected γ-amino pentanoic acid has been performed using as starting material the glutamic acid, by modification of the α-carboxylic group. The synthetic route is described in chapter five. The above route leads to the synthesis of one only γ-amino acid. Thus, a general route for the synthesis of γ-amino acids from naturally α-amino acids was studied. An α-amino acid is converted to N-protected α-amino aldehyde, which through a Wittig reaction with the appropriate ylide, is converted to N-protected α,β-unsaturated γ-amino ester. The protected γ-amino acid is obtained after catalytic hydrogenation. The above procedure was studied according to the nature of the side chain of the α-amino acid, the type of N-protecting group and finally the ylide. The optical purity of the products was verified and no racemization was found. The synthesis of C- or N-protected γ-amino acid can be achieved in a two step procedure in a very satisfactory yield by simultaneous reduction of the double bond and removal of the N- or C-protecting group. The synthetic routes of the above method are described in chapter 6. The above approach may also be applied in the synthesis of optically pure di- and tetra- amines, compounds that have been isolated by marine products and exhibit interesting biological activity. In addition, by using the appropriate ylide the synthesis of protected ε-amino acids can be achieved. These synthetic routes are reported in chapters 7 and 8.
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Ανάπτυξη μεθοδολογίας σύνθεσης οπτικά ενεργών γ-αμινοξέων και δι- και τετρα- αμινών
