Isoflucypram, the first representative of a new succinate dehydrogenase inhibitor fungicide subclass: Its chemical discovery and unusual binding mode.

Succinate dehydrogenase inhibitors (SDHIs) have played a crucial role in disease control to protect cereals as well as fruit and vegetables for more than a decade. Isoflucypram, the first representative of a newly installed subclass of SDHIs inside the Fungicide Resistance Action Committee (FRAC) family of complex II inhibitors, offers unparalleled long-lasting efficacy against major foliar diseases in cereals. Herein we report the chemical optimization from early discovery towards isoflucypram and the first hypothesis of its altered binding mode in the ubiquinone binding site of succinate dehydrogenase. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Artificial signal transduction with primary and secondary messengers.

The complete, entirely artificial, signal-transduction process was realized with a pair of tailored transmembrane units that were equipped with receptor- and reactive sites at both amphiphilic ends. Thus, docking of the primary messenger, transmission of the signal, and release of the secondary messenger could all be imitated in a single experimental setup. The system imitates the signaling principle of receptor tyrosine kinases and employs bisphosphonate head-groups for oligoamine-recognition and a pair of thiol nucleophiles and pyridine disulfide tail-groups for intravesicle S(N)2 displacement. This system operates in a unidirectional fashion, does not suffer from intervesicle competition, and is highly sensitive towards the lipid composition of the membrane and the nature of the primary messenger.

Total synthesis of dimeric pyrrole-imidazole alkaloids: sceptrin, ageliferin, nagelamide e, oxysceptrin, nakamuric acid, and the axinellamine carbon skeleton.

The dimeric pyrrole imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, high nitrogen content, and exciting bioactivities. This full account traces the evolution of a strategy that culminated in the first total syntheses of several members of this family, including sceptrin, ageliferin, nagelamide E, nakamuric acid (and its methyl ester), and oxysceptrin. Details on the fascinating conversion of sceptrin to ageliferin, which has been used to produce gram quantities of this sensitive natural product, are provided. In addition, the first enantioselective total synthesis of sceptrin and ageliferin are reported by programming the fragmentation of an oxaquadricyclane. A hallmark of our approach to this family of alkaloids is the minimal use of protecting groups despite the presence of 10 nitrogen atoms in the target compounds. Thus, the fundamental chemistry of the 2-aminoimidazole heterocycle was explored without masking its innate reactivity. Insights gained during these explorations led to total syntheses of oxysceptrin and nakamuric acid and a successful construction of the carbon skeleton of axinellamine.

Entirely artificial signal transduction with adrenaline.

Multifunctional transmembrane-building blocks with recognition sites for adrenaline on one end and the reaction partners for an SN2 reaction on the opposite end have been embedded in DPPC-liposomes. These doped vesicles can be quantitatively reduced at their disulfide head groups by externally added reducing agents; their composition and chemical processes taking place within can be monitored by NMR spectroscopy and--with limitations--by UV/Vis spectroscopy. Attempted release of thiopyridine as a second messenger into the interior of the liposome on external adrenaline addition could not be proven unambiguously because the detection system does not fulfill the necessary rigorous specificity and sensitivity requirements.

Phosphine and phosphonite complexes of a ruthenium(II) porphyrin. 1. Synthesis, structure, and solution state studies.

We have investigated the effect of complexation of different phosphorus ligands on the stability, solid state structure, and spectroscopic properties (NMR, IR, UV-vis) of a 5,15-diphenyl-substituted ruthenium porphyrin, (MeOH)Ru(II)(CO)(DPP) 2 [DPP = 5,15-bis(3',5'-di-tert-butyl)phenyl-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin]. The ligands used are PPh(3), diphenyl(phenylacetenyl)phosphine (DPAP), bis(diphenylphosphino)acetylene (DPPA), tris(phenylacetenyl)phosphine [(PA)(3)P], and diethyl (phenylacetenyl)phosphonite [PAP(OEt)(2)]. The mono-phosphine complexes (PR(3))Ru(II)(CO)(DPP) are readily formed in solution in quantitative yields. The complexes display association constants ranging from 1.2 x 10(4) M(-1) for PPh(3) to 4.8 x 10(6) M(-1) for PAP(OEt)(2). The weak association of PPh(3) does not correlate with its pK(a), delta((31)P), or cone angle value and is attributed to steric effects. Due to their kinetic lability, which is shown by 2D NMR spectroscopy, and the weakening of the carbonyl ligand via a trans effect, the mono-phosphine complexes could not be isolated. IR spectroscopy gives the relative order of pi-acceptor strength as PPh(3) < DPAP, DPPA < (PA)(3)P < PAP(OEt)(2), whereas the relative order of the sigma-donor strength is PPh(3) < (PA)(3)P < DPAP, DPPA < PAP(OEt)(2), based on the calculated pK(a) values and on the (31)P((1)H) NMR chemical shifts of the ligands. The chemical shift differences in the (31)P9(1)H)) NMR spectra upon ligand binding display a linear correlation with the calculated pK(a) values of the protonated ligands HPR(3)(+); we propose that the pK(a), and probably other electronic properties, of a specific phosphorus ligand can be estimated on the basis of the chemical shift difference Deltadelta((31)P) upon complexation to a metalloporphyrin. The bis-phosphine complexes can be isolated in pure form by crystallization from CHCl(3)-MeOH solutions using excess ligand. Association of the second ligand is in the same order of magnitude as the first binding for the phosphines, but the second phosphonite binding is decreased by a factor of about 100. The solid state structures show only marginal differences in the geometrical parameters. The calculated and the crystallographic cone angles of the ligands generally do not match, apart from the values obtained for PAP(OEt)(2).