A tale of four kingdoms – isoxazolin-5-one- and 3-nitropropanoic acid-derived natural products

Abstract

Covering up to September 2016This review reports on natural compounds that derive from the isoxazolinone ring as well as the 3-nitropropanoic acid (3-NPA) moiety. These structural elements occur in compounds that have been identified in plants, insects, bacteria and fungi. In particular, plants belonging to the family of legumes produce such compounds. In the case of insects, isoxazolin-5-one and 3-NPA derivatives were found in leaf beetles of the subtribe Chrysomelina. A number of these natural products have been synthesized so far. In the case of the single compound 3-NPA, several synthetic strategies have been reported and some of the most efficient routes are reviewed. The toxicity of 3-NPA results from its ability to bind covalently to the catalytic center of succinate dehydrogenase causing irreversible inhibition of mitochondrial respiration. As a motif that is produced by many species of plants, leaf beetles and fungi, different detoxification mechanisms for 3-NPA have evolved in different species. These mechanisms are based on amide formation of 3-NPA with amino acids, reduction to β-alanine, ester formation or oxidation to malonic acid semialdehyde. The biosynthetic pathways of 3-NPA and isoxazolin-5-one moieties have been studied in fungi, plants and leaf beetles. In the case of fungi, 3-NPA derives from aspartate, while leaf beetles use essential amino acids such as valine as ultimate precursors. In the case of plants, it is supposed that malonate serves as a precursor of 3-NPA, as indicated by feeding of C-labeled precursors to Indigofera spicata. In other leguminous plants it is suggested that asparagine is incorporated into compounds that derive from isoxazolin-5-one, which was indicated byC-labeled compounds as well. In the case of leaf beetles it was demonstrated that detection of radioactivity after C-labeling from a few precursors is not sufficient to unravel biosynthetic pathways.

Egg toxic compounds in the animal kingdom. A comprehensive review

“…29,198 The hydrolysis of the glycoside releases free 3NPA which is toxic to both vertebrates and invertebrates, acting as an irreversible inhibitor of the enzyme succinate dehydrogenase from the mitochondrial respiratory chain and being neurotoxic at least to mammals. 17…”

“…They are found in the eggs of some chrysomelid beetles. 17 3.3.6 Aristolochic acids (AAs). This is a group of nitrophenantrene carboxylic acids produced by plants and sequestered by some insects.…”

“…These compounds are found in the eggs, the hemolymph, and the adult pronotal and elytral defense glands. 17,198 The genera Gastrophysa, Chrysomela, Plagiodera, and Phratora have this toxin at two sites, within the eggs and in the yellow gluey secretion that covers the eggs. 198 However, the mechanism by which eggs are provided with these toxins is still unknown.…”

“…ref. [11][12][13] or a specic toxin class [14][15][16][17] while an integrative approach is missing. Here, we reviewed the egg toxic compounds of the animal kingdom, including both vertebrate and invertebrate phyla.…”

Novel donor-acceptor systems bearing an isoxazol-5-one core

“…The isoxazol-5(4H)-one moiety 1 is an important structural motif, present in the number of biologically active compounds, [2][3][4][5] natural products 6,7 and advanced materials. [8][9][10] By 1897, Schiff and Betti had already discovered that 4-arylmethylene-isoxazol-5-ones could be prepared by treating acetoacetic ester oxime with various aromatic aldehydes.…”