Functions and biosynthesis of plant signaling metabolites mediating plant-microbe interactions.

Covering: 2015-2022Plants and microbes have coevolved since their appearance, and their interactions, to some extent, define plant health. A reasonable fraction of small molecules plants produced are involved in mediating plant-microbe interactions, yet their functions and biosynthesis remain fragmented. The identification of these compounds and their biosynthetic genes will open up avenues for plant fitness improvement by manipulating metabolite-mediated plant-microbe interactions. Herein, we integrate the current knowledge on their chemical structures, bioactivities, and biosynthesis with the view of providing a high-level overview on their biosynthetic origins and evolutionary trajectory, and pinpointing the yet unknown and key enzymatic steps in diverse biosynthetic pathways. We further discuss the theoretical basis and prospects for directing plant signaling metabolite biosynthesis for microbe-aided plant health improvement in the future.

BAR-based optimum adaptive steered MD for configurational sampling.

The equilibrium and nonequilibrium adaptive alchemical free energy simulation methods optimum Bennett's acceptance ratio and optimum crooks' equation (OCE), based on the statistically optimal bidirectional reweighting estimator named Bennett's Acceptance Ratio or Crooks' equation, perform initial sampling in the staging alchemical transformation and then determine the importance rank of different states via the time-derivative of the variance. The method is proven to give speedups compared with the equal time rule. In the current work, we extend the time derivative of variance guided adaptive sampling method to the configurational space, falling in the term of steered MD (SMD). The SMD approach biasing physically meaningful collective variable (CV) such as one dihedral or one distance to pulling the system from one conformational state to another. By minimizing the variance of the free energy differences along the pathway in an optimized way, a new type of adaptive SMD (ASMD) is introduced. As exhibits in the alchemical case, this adaptive sampling method outperforms the traditional equal-time SMD in nonequilibrium stratification. Also, the method gives much more efficient calculation of potential of mean force than the selection criterion-based ASMD scheme, which is proven to be more efficient than traditional SMD. The OCE workflow is periodicity-of-CV dependent while ASMD is not. The performance is demonstrated in a dihedral flipping case and two distance pulling cases, accounting for periodic and nonperiodic CVs, respectively. © 2019 Wiley Periodicals, Inc.

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin.

Herein, we describe a biomimetic entry to (+)-3-hydroxymethylartemisinin (2) as well as to the artemisinin derivatives (+)-3-hydroxymethyl-9-desmethylartemisinin (16) and (+)-3-hydroxymethyl-9-epi-artemisinin (18), starting from the known and readily available chiral aldehyde 3 and alkyne 4. Subsequently, the synthesized compounds have been evaluated for their antimalarial activity against the drug-sensitive P. falciparum NF54 strain. All of them were inactive. In addition, they did not show any toxicity against L6 cells (a primary cell line derived from rat skeletal myoblasts). These results contribute to a better understanding of artemisinins mechanism of action.

BAR-based optimum adaptive sampling regime for variance minimization in alchemical transformation: the nonequilibrium stratification.

Following the previously proposed equilibrate-state sampling based adaptive sampling regime Optimum Bennett Acceptance Ratio (OBAR), we introduce its nonequilibrium extension, the Optimum Crooks' Equation (OCE) in the current work. The efficiency of the NonEquilibrium Work (NEW) stratification is improved by adaptively manipulating the significance of each nonequilibrium realization followed by importance sampling. As is exhibited in the equilibrium case, the nonequilibrium extension outperforms the simple equal time rule used in nonequilibrium stratification in the sense of minimizing the total variance of the free energy estimate. The speedup of this non-equal time rule is more than 1-fold. The Time Derivative of total Variance (TDV) proposed for the OBAR criterion is extended to determine the importance of each nonequilibrium transformation, which is linearly dependent on the variance. The TDV in the nonequilibrium case gives a totally different importance rank from the standard errors of the free energy differences and OBAR TDV due to the duration of nonequilibrium pulling being added into the OCE equation. The performance of the OCE workflow is demonstrated in the solvation of several small molecules with a series of lambda increments and relaxation times between successive perturbations. To the best of our knowledge, such a nonequilibrium adaptive sampling regime in alchemical transformation is unprecedented.

Palladium-catalyzed C-N cross coupling of sulfinamides and aryl halides.

The palladium-catalyzed C-N cross coupling of sulfinamides and aryl halides is reported. In the presence of Pd(2)(dba)(3), tBuXPhos, NaOH, and a small amount of water, the C-N cross coupling of chiral tert-butanesulfinamide and aryl halides was accomplished to give N-aryl tert-butanesulfinamide without racemization, and the coupling of racemic p-toluenesulfinamide smoothly afforded N-aryl p-toluenesulfinamides. 2-Bromopyridine was also suitable for the coupling. Addition of a small amount of water to the catalytic system was of importance to obtain high yields.

(R)-N-(3-Meth-oxy-phen-yl)-tert-butane-sulfinamide.

The title compound, C(11)H(17)NO(2)S, was obtained by the reaction of (R)-tert-butane-sulfinamide with 3-meth-oxy-phenyl bromide in toluene. In the crystal, mol-ecules inter-act head-to-tail through N-H⋯O and C-H⋯O hydrogen bonds, forming one-dimensional chains parallel to the a axis.

Synthesis of phenothiazines via ligand-free CuI-catalyzed cascade C-S and C-N coupling of aryl ortho-dihalides and ortho-aminobenzenethiols.

A ligand-free CuI-catalyzed cascade C-S and C-N cross coupling of (hetero)aryl ortho-dihalides and ortho-aminobenzenethiols has been developed, and various phenothiazines were synthesized with excellent regioselectivity. A possible mechanism is proposed for the cascade coupling.