The “Normalizing Factor” for the Tomato Mutant chloronerva. XXIII. Deaminonicotianamine and 2‐Decarboxynicotianamine

Abstract

AbstractDeaminonicotianamine (8) and 2‐decarboxynicotianamine (11) were synthesized by stepwise reductive alkylation of (S)‐2‐ethoxycarbonylazetidine (3) or azetidine (9) with ethyl (S)‐4‐oxo‐2‐(trifluoroacetylamino)butanoate (4) and ethyl 4‐ oxobutanoate (7), respectively. The amino acids 8 or 11 as well as the intermediates, (2S,αS)‐α‐amino‐2‐carboxy‐1‐azetidinebutanoic acid (6) and (S)‐α‐amino‐1‐azetidinebutanoic acid (10) did not show biological activity with regard to chlorophyll synthesis in chlorotic leaflets of the tomato mutant chloronerva. The compound 11 promoted the normally inhibited root growth of the mutant.Nicotianamine (1) has been identified as the “normalizing factor” which restores chlorophyll synthesis, growth and development of the auxotroph mutant chloronerva of Lycopersicon esculentum Mill. [2]. Nicotianamine proved to be widespread in the plant kingdom ([1], cf. [3]). Biochemical experiments revealed a disturbed iron metabolism of the mutant, leading to an excessive iron absorption by the roots on the one hand and an irregular iron distribution within young leaves on the other [4, 5]. Nicotianamine (1) forms stable 1:1 complexes with iron (II) and other bivalent metal ions [6] with high stability constants in comparison with those of bidentate amino acids; e.g. the stability constants for the 1:1 copper complexes of nicotianamine and α‐alanine are 1018.6 [6] and 108.5 [7], respectively. As is evident from a Dreiding model, nicotianamine has an optimal molecular structure for complex formation with metal ions. Not only are six functional groups present, necessary for octahedral coordination, but the distances between the groups are also optimal for the formation of chelate rings: three 5‐membered rings formed by the α‐amino acid residues and two 6‐membered rings formed by the 1,3‐diaminopropane moieties [2, 3]. In order to study whether strong complex formation is important for the biological activity of nicotianamine, a series of synthetic analogues were prepared. The antipode of nicotianamine [8] and the proline analogue [9] were biologically active, further analogues, e.g. homologues with 1,4‐diaminobutane moieties [10], peptides [11] or quadridentate ligands [2, 8, 10] proved to be inactive. The hitherto existing results indicate that a partial structure 2 (or enantiomeric) is essential for the biological activity and that nicotianamine plays an important role in the cellular iron transport and/or metabolism in plants.