Synthesis of pyrazole containing α-amino acids via a highly regioselective condensation/aza-Michael reaction of β-aryl α,β-unsaturated ketonesElectronic supplementary information (ESI) available: Experimental procedures and data for all known compounds and NMR spectra for all new compounds. See DOI: 10.1039/c5ob00364d

• Main Authors: Gilfillan, Lynne, Artschwager, Raik, Harkiss, Alexander H, Liskamp, Rob M. J, Sutherland, Andrew
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob00364d

A synthetic approach for the preparation of a new class of highly conjugated unnatural α-amino acids bearing a 5-arylpyrazole side-chain has been developed. Horner-Wadsworth-Emmons reaction of an aspartic acid derived β-keto phosphonate ester with a range of aromatic aldehydes gave β-aryl α,β-unsaturated ketones. Treatment of these with phenyl hydrazine followed by oxidation allowed the regioselective synthesis of pyrazole derived α-amino acids. As well as evaluating the fluorescent properties of the α-amino acids, their synthetic utility was also explored with the preparation of a sulfonyl fluoride derivative, a potential probe for serine proteases. A new class of α-amino acid incorporating 5-aryl pyrazole units have been prepared using a highly regioselective condensation/aza-Michael reaction of β-aryl α,β-unsaturated ketones.