The N-alkylated indanylidenepyrroline (NAIP) Schiff base 3 is an unnatural a-amino acid precursor potentially useful for the preparation of semisynthetic peptides and proteins incorporating charged side chains whose structure can be modulated via Z/E photoisomerization. Here we report that the heteroallylic protons of 3 led to partial loss of ethanol accompanied by formation of the novel heterocyclic system 4 during attempted deprotection. We also show that the same protons catalyze the thermal isomerization of 3, making the light-driven conformational control concept ineffective for times longer than a few hours. These problems are not present in the previously unreported compound 5 where the acidic methyl group is replaced by an H atom. Therefore, 5, rather than 3, constitutes a promising prototype for the design of building blocks capable to modulate the electrostatic potential of a protein in specific locations via light irradiation.
Paccani, Riccardo Rossi; Donati, Donato; Fusi, Stefania; Latterini, Loredana; Farina, Grazia; Zanirato, Vinicio; and Olivucci, Massimo, "Toward A Stable Alpha-cycloalkyl Amino Acid With A Photoswitchable Cationic Side Chain" (2012). Chemistry Faculty Publications. 66.
Journal Of Organic Chemistry