1390659-83-2Relevant academic research and scientific papers
Synthesis of enantiopure 7-substituted azepane-2-carboxylic acids as templates for conformationally constrained peptidomimetics
Cini, Elena,Bifulco, Giuseppe,Menchi, Gloria,Rodriquez, Manuela,Taddei, Maurizio
, p. 2133 - 2141 (2012/06/01)
The introduction of a cyclic amino acid in a peptide is one of the best methods to rigidify a strand. A general approach towards a new class of seven-membered ring amino acids is described starting from (S)-tribenzyl glutamic acid γ-aldehyde, which reacts with β-keto phosphonates to generate the Horner-Wadsworth-Emmons product. In the presence of H2 and a Pd catalyst, a four-step process occurs involving double-bond hydrogenation, hydrogenolysis of three benzyl protecting groups, imine formation, and reductive amination to produce the 7-substituted azepane carboxylic acid in good overall yield and with good to excellent diastereomeric ratios. An amino function can be introduced in the 7-position as an additional orthogonal chemical handle for readily generating diversity on the cyclic amino acid scaffold by using a β-keto phosphonate derived from amino acids. A cyclic RGD (Arg-Gly-Asp) pentapeptide analogue containing this new class of noncoded amino acids was also prepared by microwave-assisted cyclization, showing a promising activity as αvβ3 integrin inhibitor.
