Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004-2024.

The increasing importance of azaheterocyclic phosphonates in the agrochemical, synthetic, and medicinal field has provoked an intense search in the development of synthetic routes for obtaining novel members of this family of compounds. This updated review covers methodologies established since 2004, focusing on the synthesis of azaheterocyclic phosphonates, of which the phosphonate moiety is directly substituted onto to the azaheterocyclic structure. Emphasizing recent advances, this review classifies newly developed synthetic approaches according to the ring size and providing information on biological activities whenever available. Furthermore, this review summarizes information on various methods for the formation of C-P bonds, examining sustainable approaches such as the Michaelis-Arbuzov reaction, the Michaelis-Becker reaction, the Pudovik reaction, the Hirao coupling, and the Kabachnik-Fields reaction. After analyzing the biological activities and applications of azaheterocyclic phosphonates investigated in recent years, a predominant focus on the evaluation of these compounds as anticancer agents is evident. Furthermore, emerging applications underline the versatility and potential of these compounds, highlighting the need for continued research on synthetic methods to expand this interesting family.

Diproline-induced resistance to parasitic nematodes in the same and subsequent rice generations: Roles of iron, nitric oxide and ethylene.

Induced resistance (IR) is a plant phenotype characterized by lower susceptibility to biotic challenges upon elicitation by so-called IR stimuli. Earlier, we identified diproline (cyclo(l-Pro-l-Pro)) as IR stimulus that protects rice (Oryza sativa) against the root-knot nematode Meloidogyne graminicola (Mg). In the current study, detailed transcriptome analyses at different time points, and under uninfected and nematode-infected conditions revealed that this rice IR phenotype is correlated with induction of genes related to iron (Fe), ethylene (ET) and reactive oxygen species (ROS)/reactive nitrogen species (RNS) metabolism. An infection experiment under Fe limiting conditions confirmed that diproline-IR is only effective under optimal Fe supply. Although total root Fe levels were not affected in diproline-treated plants, phytosiderophore secretion was found to be induced by this treatment. Experiments on mutant and transgenic rice lines impaired in ET or ROS/RNS metabolism confirmed that these metabolites are involved in diproline-IR. Finally, we provide evidence for transgenerational inheritance of diproline-IR (diproline-TIR), as two successive generations of diproline-treated ancestors exhibited an IR phenotype while themselves never being exposed to diproline. Transcriptome analyses on the offspring plants revealed extensive overlap between the pathways underpinning diproline-IR and diproline-TIR. Although diproline induces significant systemic changes in global DNA methylation levels early after treatment, such changes in DNA methylation were not detected in the descendants of these plants. To our knowledge, this is the first report of TIR in rice and the first transcriptional assessment of TIR in monocots.

Altering the Sex Pheromone Cyclo(l-Pro-l-Pro) of the Diatom Seminavis robusta towards a Chemical Probe.

As a major group of algae, diatoms are responsible for a substantial part of the primary production on the planet. Pennate diatoms have a predominantly benthic lifestyle and are the most species-rich diatom group, with members of the raphid clades being motile and generally having heterothallic sexual reproduction. It was recently shown that the model species Seminavis robusta uses multiple sexual cues during mating, including cyclo(l-Pro-l-Pro) as an attraction pheromone. Elaboration of the pheromone-detection system is a key aspect in elucidating pennate diatom life-cycle regulation that could yield novel fundamental insights into diatom speciation. This study reports the synthesis and bio-evaluation of seven novel pheromone analogs containing small structural alterations to the cyclo(l-Pro-l-Pro) pheromone. Toxicity, attraction, and interference assays were applied to assess their potential activity as a pheromone. Most of our analogs show a moderate-to-good bioactivity and low-to-no phytotoxicity. The pheromone activity of azide- and diazirine-containing analogs was unaffected and induced a similar mating behavior as the natural pheromone. These results demonstrate that the introduction of confined structural modifications can be used to develop a chemical probe based on the diazirine- and/or azide-containing analogs to study the pheromone-detection system of S. robusta.

Mating type specific transcriptomic response to sex inducing pheromone in the pennate diatom Seminavis robusta.

Sexual reproduction is a fundamental phase in the life cycle of most diatoms. Despite its role as a source of genetic variation, it is rarely reported in natural circumstances and its molecular foundations remain largely unknown. Here, we integrate independent transcriptomic datasets to prioritize genes responding to sex inducing pheromones (SIPs) in the pennate diatom Seminavis robusta. We observe marked gene expression changes associated with SIP treatment in both mating types, including an inhibition of S phase progression, chloroplast division, mitosis, and cell wall formation. Meanwhile, meiotic genes are upregulated in response to SIP, including a sexually induced diatom specific cyclin. Our data further suggest an important role for reactive oxygen species, energy metabolism, and cGMP signaling during the early stages of sexual reproduction. In addition, we identify several genes with a mating type specific response to SIP, and link their expression pattern with physiological specialization, such as the production of the attraction pheromone diproline in mating type - (MT-) and mate-searching behavior in mating type + (MT+). Combined, our results provide a model for early sexual reproduction in pennate diatoms and significantly expand the suite of target genes to detect sexual reproduction events in natural diatom populations.

The Use of PTI-Marker Genes to Identify Novel Compounds that Establish Induced Resistance in Rice.

Compounds that establish induced resistance (IR) in plants are promising alternatives for the pesticides that are progressively being banned worldwide. Screening platforms to identify IR-establishing compounds have been developed, but none were specifically designed for monocot plants. Here, we propose the use of an RT-qPCR screening platform, based on conserved immunity marker genes of rice as proxy for IR induction. Central regulators of biotic stress responses of rice were identified with a weighted gene co-expression network analysis (WGCNA), using more than 350 microarray datasets of rice under various sorts of biotic stress. Candidate genes were narrowed down to six immunity marker genes, based on consistent association with pattern-triggered immunity (PTI), both in rice plants as in rice cell suspension cultures (RCSCs). By monitoring the expression of these genes in RCSCs upon treatment with candidate IR-inducing compounds, we showed that our marker genes can predict IR induction in rice. Diproline, a novel IR-establishing compound for monocots that was detected with these marker genes, was shown to induce rice resistance against root-knot nematodes, without fitness costs. Gene expression profiling of the here-described PTI-marker genes can be executed on fully-grown plants or in RCSCs, providing a novel and versatile tool to predict IR induction.