Access to New Cytotoxic Quinone-Amino Acid Conjugates Linked through A Vinylic Spacer from 2-Acylnaphthoquinones and Methyl 3-Aminocrotonate.

The reaction of 2-acetyl- and 2-benzoyl-1,4-naphthoquinone with ()-methyl 3-(hydroxymethyl)aminocrotonate proceeds through a formal [3+3] process to yield the corresponding 1,2-dihydrobenzisoquinolinequinones in 63% and 72% yield, respectively. The reactions of 2-acyl-1,4-naphthoquinone with enaminones, derived from diverse l- and d-amino acid methyl esters, produced the corresponding naphthoquinone amino acids conjugates bonded through a vinyl spacer in the yields range 40-71%. The presence of not-separable isomers of the naphthoquinone amino acids conjugates in the ¹H- and C-NMR spectra is explained by the existence of conformational isomers generated by hindered rotation of the substituent bonded to the quinone double bond.