Synthesis of pyrazole containing α-amino acids via a highly regioselective condensation/aza-Michael reaction of β-aryl α,β-unsaturated ketones?

Organic & Biomolecular Chemistry Pub Date: 2015-03-10 DOI: 10.1039/C5OB00364D

Abstract

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.

Graphical abstract: Synthesis of pyrazole containing α-amino acids via a highly regioselective condensation/aza-Michael reaction of β-aryl α,β-unsaturated ketones
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