Synthesis of Branched Alpha- And Beta-Amino Acids. Using C-Nucleophile Additions to Imines and Nitrones

Artificial peptides, containing alpha- and/or beta-amino acids with bulky substituents, can potentially possess some unusual properties, for example, decreased conformational ability or formation of stable secondary structures. Therefore, the preparation of such unnatural amino acids is of high interest. In this thesis, a route to enantiomerically pure 1-adamantylglycine was developed. The crucial step was the highly stereoselective addition of adamantylmagnesium bromide to the C=N bond of 2,3-O-cyclohexylidene-D-glyceraldehyde N-benzylnitrone effected in the presence of Lewis acid. Finally, 1-adamantylglycine was synthesized in 28 % yield over 6 steps. The routes to 9-aminofluorenylacetic and beta-aminobeta, beta-diphenylpropionic acids were proposed and they consist in the addition of allyl Grignard reagents to imines with various protecting groups, followed by oxidative transformation of the allyl group. Also some procedures for the preparation of 3,3-disubstituted 4-azetidinones, direct precursors of the corresponding beta-branched beta-amino acids, have been investigated.