Oxidative Phosphonylation of Aromatic Compounds

Abstract

Aryl phosphonates can be prepared in good yields from the respective arenes and tri- or dialkylphosphites by either chemical or electrochemical oxidation^1. The anodic oxidation proceeds either via phosphonium radical cations which then attack the arenes electrophilically or via arene radical cations which add the trialkyl-phosphite as nucleophile^1,2. Aryl phosphonates are also obtained in good yields by chemical oxidation with peroxidisulfate/AgNO₃, Iron(III)- or Cerium(IV)-complexes in acetonitrile/water or glacial acetic acid^3.     

三种天然脱氧核苷的高效合成

本文以1-氯-2-脱氧-α-3,5-二-O-(对氯苯甲酰基)呋喃核糖(1)(以下简称氯代糖)为原料, 开发出可以适用于大规模工业生产的简单、 高效的合成上述三种天然核苷路线.     

Phosphonylation of a polypentenamer and preparation of its hydrogenated derivatives

Phosphonylated derivatives of a polypentenamer (PP) containing 82% trans and 17% cis double bonds have been prepared by the free-radical addition of dimethylphosphite to the double bonds and subsequent hydrogenation of the residual unsaturation. In this way derivatives were prepared containing approximately 5 and 10 mole % dimethylphosphonate side groups. These side groups were further reacted by hydrolysis or neutralization to form phosphonic acid and cesium phosphonate salts. Reaction conditions were so chosen that no backbone degradation occurred, and side reactions leading to crosslinking were avoided. The derivatives were characterized by gel-permeation chromatography (GPC), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy, and nuclear magnetic resonance spectroscopy. It was found that increasing substituent concentration decreases the melting point T_m in the case of the hydrogenated derivatives and increases the glass transition temperature T_g in the case of the unhydrogenated derivatives. The free acid derivatives are the least thermally stable of all those studied and the hydrogenated derivatives are generally more stable than the unhydrogenated derivatives.     

Phosphonylation mechanisms of sarin and acetylcholinesterase: a model DFT study

Potential energy surfaces for the phosphonylation of sarin and acetylcholinesterase (AChE) have been theoretically studied at the B3LYP/6-311G(d,p) level of theory. The obtained results show that the phosphonylation process involves a two-step addition-elimination mechanism, with the first step (addition process) being the rate-determining step, while by comparison, the ensuing steps are very rapid. Stable trigonal bipyramidal intermediates are formed in the studied pathways. It is also revealed that the catalytic triad of acetylcholinesterase plays the catalytic role in the reaction by speeding up the phosphonylation process, as it does in the acylation reaction of ACh and AChE. The effect of aqueous solvation was accounted for via the polarizable continuum model. It is concluded that the enzymatic reaction here is influenced strongly by the solvent environment.     

Synthesis,Phosphonylation, and Anti-Viral Activity of Some 6-Aryl-5-cyano-2-thiouracils

Russian Journal of General Chemistry - A series of 6-aryl-5-cyano-2-thiouracils was synthesized, the reaction of which with diethyl chloroethynylphosphonate leads to the selective formation of new...     

Phosphonylation Controls the Protein Corona of Multifunctional Polyglycerol‐Modified Nanocarriers

Nanocarriers are a platform for modern drug delivery. In contact with blood, proteins adsorb to nanocarriers, altering their behavior in vivo. To reduce unspecific protein adsorption and unspecific cellular uptake, nanocarriers are modified with hydrophilic polymers like poly(ethylene glycol) (PEG). However, with PEG the attachment of further functional structures such as targeting units is limited. A method to introduce multifunctionality via polyglycerol (PG) while maintaining the hydrophilicity of PEG is introduced. Different amounts of negatively charged phosphonate groups (up to 29 mol%) are attached to the multifunctional PGs (M_n 2–4 kg mol^?1, Ð < 1.36) by post‐modification. PGs are used in the miniemulsion/solvent evaporation procedure to prepare model nanocarriers. Their behavior in human blood plasma is investigated to determine the influence of the negative charges on the protein adsorption. The protein corona of PGylated nanocarriers is similar to PEGylated analogs (on same nanocarriers), but the protein pattern could be gradually altered by the integration of phosphonates. This is the first report on the gradual increase of negative charges on nanocarriers and intriguingly up to a certain amount of phosphonate groups per nanocarrier the protein pattern remains relatively unchanged, which is important for the future design of nanocarriers.     

酶解液中脱氧核苷的高效液相色谱测定

本文介绍了酶解液中脱氧核苷的高效液相色谱（ＨＰＬＣ）测定法，阴离子交换树脂用作固相萃取剂除去酶解液中对脱氧核苷测定有干扰的脱氧核苷酸，考察了介质ｐＨ，萃取剂用量等对测定的影响，方法简便，正确快速，可应用到脱氧核苷生产工艺。     

Biomimetic seleninates and selenonates

The synthesis of a variety of pyranose-, nucleoside-, (amino acid)-, and polyhydric-based seleninic and selenonic acids by DMDO oxidation of the corresponding selenoesters is reported, as well as some unusual coupling reactions of the seleninate and selenonate functionality with biological nucleophilic groups (sulfhydryl, indole, phenol, imidazole, carboxamide) that are found in proteins and enzyme active sites.     

Biomimetic selectivity

Synthetic organic chemistry normally achieves selectivity by manipulation of the intrinsic reactivity of the substrate, but enzyme use is quite a different principle. The geometry of the enzyme-substrate complex determines enzymatic selectivity, completely overwhelming any normal selective reactivities. Biomimetic chemistry aims to imitate the enzymatic style. Some early approaches used attached reagents or templates to direct photochemical and free radical processes, with a combination of geometric and reactivity control. Recent work uses a mimic of the enzyme class cytochrome P-450 to achieve the selective hydroxylations of steroids with complete domination by the geometry of the catalyst-substrate complex.     

微制造技术与仿生壁虎腿

壁虎甚至在真空中都可以在垂直光滑的玻璃墙壁上纹丝不动和爬行,显然,这不可能是摩擦力和真空吸力所致,它不分泌任何液体,也不可能是通常的粘合剂作用。对壁虎脚足刚毛吸力的精确测定表明,壁虎腿与物体表面的吸力完全是范德华力相互作用。本文详细介绍了有关壁虎腿仿生研究的最新进展和可能的制备壁虎胶带的微制造方法。     

Biomimetic smart nanopores and nanochannels

Nature provides a huge range of biological materials, just as ion channels, with various smart functions over millions of years of evolution, and which serve as a big source of bio-inspiration for biomimetic materials. In this critical review, a strategy for the design and synthesis of biomimetic smart nanopores and nanochannels is presented and put into context with recent progress in this rapidly growing field from biological, inorganic, organic to composite nanopore and nanochannel materials, which can respond to single/multiple external stimuli, e.g., pH, temperature, light, and so on. This review is intended to utilize a specific responsive behavior for regulating ionic transport properties inside the single nanopore or nanochannel as an example to demonstrate the feasibility of the design strategy, and provide an overview of this fascinating research field (109 references).     

Biomimetic Radical Chemistry and Applications

Some of the most interesting aspects of free radical chemistry that emerged in the last two decades are radical enzyme mechanisms, cell signaling cascades, antioxidant activities, and free radical-induced damage of biomolecules. In addition, identification of modified biomolecules opened the way for the evaluation of in vivo damage through biomarkers. When studying free radical-based chemical mechanisms, it is very important to establish biomimetic models, which allow the experiments to be performed in a simplified environment, but suitably designed to be in strict connection with cellular conditions. The 28 papers (11 reviews and 17 articles) published in the two Special Issues of Molecules on “Biomimetic Radical Chemistry and Applications (2019 and 2021)” show a remarkable range of research in this area. The biomimetic approach is presented with new insights and reviews of the current knowledge in the field of radical-based processes relevant to health, such as biomolecular damages and repair, signaling and biomarkers, biotechnological applications, and novel synthetic approaches.     

Biomimetic and Biocatalytic Synthesis of Bruceol

The first total synthesis of bruceol has been achieved using a biomimetic cascade cyclization initiated by a stereoselective Jacobsen–Katsuki epoxidation (and kinetic resolution) of racemic protobruceol‐I. A bacterial cytochrome P450 monooxygenase was also found to catalyze the conversion of protobruceol‐I into bruceol. The first full analysis of the NMR data of natural bruceol suggested that “isobruceol” was a previously unrecognized natural product also isolated from Philotheca brucei. This was confirmed by the re‐isolation, synthesis, and X‐ray analysis of isobruceol. In total, eight stereoisomers and structural isomers of bruceol have been synthesized in a highly divergent approach.     

Biomimetic Extreme-Temperature- and Environment-Adaptable Hydrogels

Recently, temperature-resistant hydrogels, hydrogels which are freezing- and dehydration-resistant, have garnered considerable attention in the scientific community as they extend the rage of application of hydrogels to arid and/or cold environments. Besides, these hydrogels exhibit tunable conductivity and mechanical performance while offering excellent biocompatibility and flexibility, making them interesting candidates for flexible and wearable electronics and (bio)sensors. Several biomimetic strategies were developed to fabricate anti-freezing and anti-dehydration hydrogels with a diversity of merits, such as high strain resistance and conductivity, even at sub-zero temperatures, and employed as (bio)sensors, electrodes, and energy-storage devices. This review summarizes the recent advances in the preparation and application of temperature-resistant hydrogels, indicates issues of the state-of-the-art hydrogels, and offers potential future research directions.     

Biomimetic synthesis of hyperolactones

Through a biomimetic pathway, hyperolactone D, 4-hydroxyhyperolactone D, and hyperolactone C were synthesized from methyl acetoacetate via Weiler's dianion method, asymmetric allylic alkylation, biomimetic lactonization, oxidation, and cyclization. The stereochemistry of the quaternary carbon was controlled efficiently by Palladium-catalyzed asymmetric allylic alkylation. This strategy was also used for the synthesis of hyperolactone B.     

Biomimetic synthesis of biatractylolide and biepiasterolide

[reaction: see text] The biomimetic synthesis of the bisesquiterpenoids biatractylolide 1 and biepiasterolide 2 is reported.