Synthesis of Phosphorus-Containing Carboxylic Acid Derivatives

Abstract

Phosphorus-containing carboxylic acids are of great interest as potential antiviral substances (1). Thus, the search for the simple and technological methods of their synthesis draws much attention.     

Identification of Pharmacophoric Fragments of DYRK1A Inhibitors Using Machine Learning Classification Models

Dual-specific tyrosine phosphorylation regulated kinase 1 (DYRK1A) has been regarded as a potential therapeutic target of neurodegenerative diseases, and considerable progress has been made in the discovery of DYRK1A inhibitors. Identification of pharmacophoric fragments provides valuable information for structure- and fragment-based design of potent and selective DYRK1A inhibitors. In this study, seven machine learning methods along with five molecular fingerprints were employed to develop qualitative classification models of DYRK1A inhibitors, which were evaluated by cross-validation, test set, and external validation set with four performance indicators of predictive classification accuracy (CA), the area under receiver operating characteristic (AUC), Matthews correlation coefficient (MCC), and balanced accuracy (BA). The PubChem fingerprint-support vector machine model (CA = 0.909, AUC = 0.933, MCC = 0.717, BA = 0.855) and PubChem fingerprint along with the artificial neural model (CA = 0.862, AUC = 0.911, MCC = 0.705, BA = 0.870) were considered as the optimal modes for training set and test set, respectively. A hybrid data balancing method SMOTETL, a combination of synthetic minority over-sampling technique (SMOTE) and Tomek link (TL) algorithms, was applied to explore the impact of balanced learning on the performance of models. Based on the frequency analysis and information gain, pharmacophoric fragments related to DYRK1A inhibition were also identified. All the results will provide theoretical supports and clues for the screening and design of novel DYRK1A inhibitors.     

Phosphorus-Containing Dendrimers: Synthesis and Properties

Several series of phosphorus-containing dendrimers have been designed to study the variation of their properties, depending on the type, the location (surface, branches, core, and cavities), and the number of functions implied.     

Synthesis and Properties of Phosphorus-Containing Aromatic Polyethers

The phosphorus-containing aromatic polyethers were prepared from bis(p-chlorophenyl)phenylphosphine oxide (BCPO) with the sodium salt of several bisphenols by high temperature solution polycondensation. The best result (yield 84%, n _sp /c = 0.15) was obtained from BCPO with bisphenol A (BPA) in dimethyl sulfoxide. However, the polymerization in the solvents such as N, N′-dimethyl-2-pyrrolidone, hexamethylphosphoramide, and N,N′-dimethylformamide, and the polymerization with the other bisphenols HO-C₆H₄-X-C₆H₄?OH, where X = CO, S0₂, CH₃P(O), C₆H₅P(O) in place of BPA gave gumlike polymers. The polymer prepared from BCPO and BPA did not decompose up to ca. 300°C under air or nitrogen atmosphere, but it decomposed slowly at 300–520°C, and decomposed rapidly at 520–540°C. The activation energy (δE) for the maximum rate of weight loss was 47.8 kcal/mole.     

Synthesis of Biological Activities of Phosphorus-Containing Polycationic Strings

Abstract

Several series of phosphoruscontaining polycationic strings have been prepared. These include those in which quaternary phosphonium sites are located at regular intervals along a linear chain of defined length (“Strings”), and those in which the cationic phosphonium, sites are in linkages arrayed in branching arms about a cenhal focus unit (“baloons”). Polyphosphonium “balloon” arrays have been attached to a polystyrene backbone prowding a mataial which serves as an anionic exchange resin. PolyCationic strings have been prepared in which phosphorus is present a3 phosphine oxide functidties and the cationic sites are quatanary ammonium sites anayed at regular intervals along a linear chain of defined length. Several of the resultant materials have demonshated sigruficant antibaaaial activity. Interactions of the polycationic species with the anionic gmove region of double stranded DNA have been investigated.     

Catalytic Synthesis of Phosphorus-Containing Extractant: Tributyl Phosphate

Russian Journal of Applied Chemistry - By kinetics, volumetry, gas chromatography, elemental analysis, IR, NMR spectroscopy the oxidative alkoxylation of yellow phosphorus to phosphorus esters in...     

Synthesis of Homogalacturonan Fragments

ABSTRACT

Glycosylation of the D-galacturonic acid ester derivatives 15 and 17, which are prepared directly from D-galacturonic acid, with the thioglycosides 28 and 32, derived from the same sugar, provides α(1→4)-linked dimers. The formation of the glycosidic linkage between the galacturonic acid moieties is best achieved by iodonium di-sym-collidine perchlorate promotion. Thus, the 4'-O-p-methoxybenzyl dimer 38 can be obtained in 64% yield. Partial deprotection of the 4'-O-position provided the glycosyl acceptor 36, which was coupled with the donor 32 to yield the α(1”→4')-linked trimer 39 (48%). Approximately 8% of the β(1”→4')-coupled isomer was observed in the ¹³C NMR spectrum of the reaction mixture.     

Synthesis and Characterization of DNA Fragments Bearing an Adenine Radiation Product: 7,8-Dihydroadenin-8-one

The 7,8-dihydroadenin-8-one is one of the base derivatives formed by the action of ionizing radiation upon DNA. In order in investigate the mutagenic effects and the repair of DNA lesions induced by gamma rays, the synthesis of oligonucleotides bearing this damage has been performed by the phosphoramidite methodology. The preparation of the corresponding protected mononucleotide 6 (see Scheme) and its insertion into a DNA fragment are described. The modified oligonucleotide was purified by HPLC, characterized by DNA sequencing, enzymatic hydrolysis, and FAB mass spectrometry. In the experimental conditions used herein, no basic or acidic degradation was observed. In the DNA chain, the lesion is stable on piperidine heating under the usual DNA sequencing conditions.     

有机磷类阻燃剂的合成及应用进展

由于有机磷阻燃剂具有高效、低毒、无污染及无烟等特点,该领域的研究在国内外得到极大的关注,已经在合成和应用等方面取得了显著成就。 本文对磷系阻燃剂的阻燃机理及近年来磷系阻燃剂的应用进展作了简要综述。 分别综述了各类有机含磷阻燃剂的研究进展,并提出了有机磷阻燃剂今后的发展方向。     

Synthesis of Rhamnogalacturonan I Fragments

ABSTRACT

The partially deprotected trisaccharide 17 has been synthesized as an analogue of the repeating unit of the backbone of rhamnogalacturonan I. The trisaccharide 17 was obtained after prior selective derivatization of HO-3 and HO-4 of a rhamnopyranose cyanoethylidene glycosyl donor, followed by coupling with a tritylated galactopyranosyluronic acceptor (11), selective removal of the acetyl group at the O-2' position of the formed disaccharide 12, and glycosylation of the HO-2' position with methyl (ethyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-1-thio-β-D-galactopyranosid)uronate (14) providing methyl (methyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-α-D-galactopyranosyluronate)-(1→2)-(4-O-benzoyl-3-O-benzyl-α-L-rhamnopyranosyl)-(1→4)-(allyl 2,3-di-O-benzyl-β-D-galactopyranosid)uronate (15). Finally, palladium chloride catalyzed deallylation (16) and hydrogenolysis over Pd-C resulted in methyl (methyl α-D-galactopyranosyluronate)-(1→2)-(4-O-benzoyl-α-L-rhamnopyranosyl)-(1→4)-α/β D-galactopyranuronate (17).     

壳聚糖含磷衍生物的合成、表征及其应用研究

壳聚糖是一种可再生的天然碱性多糖,具有多种优良的特性。但是,由于壳聚糖本身的溶解性很差,只能溶解在一些稀酸中,这就在一定程度上限制了其进一步的研究与应用。因此,通过修饰改性提高其已有功能、赋予新的功能是壳聚糖重要的研究领域。其中,通过磷酸化或磷酰化改性是壳聚糖改性研究的方向之一。本文综述了在壳聚糖链上引入含磷/膦基团合成壳聚糖含磷衍生物的研究进展;介绍并讨论了壳聚糖含磷衍生物的合成及纯化方法;对壳聚糖含磷衍生物结构、性能及表面形貌的表征进行了详细的阐述;对壳聚糖含磷衍生物的应用进行了总结,并展望了壳聚糖含磷衍生物未来的应用前景。     

Synthesis of Aminomethylphosphines with Triazaadamantane Fragments

The reaction of (hydroxymethyl)diphenylphosphine with 7-amino-1,3,5-triazaadamantane, followed by ready oxidation of the initially formed aminomethylphosphine gave diphenyl[(1,3,5-triazaadamantan-7-yl)aminomethyl]phosphine oxide. The reactions of bis(hydroxymethyl)phenylphosphine with 2 mol of 7-amino-1,3,5-triazaadamantane in the absence and in the presence of Paraform provided bis[(1,3,5-triazaadamantan-7-yl)aminomethyl]phenylphosphine and 1,3-bis(1,3,5-triazaadamantan-7-yl)-5-phenyl-1,3,5-diazaphosphorinane, respectively.     

Organocatalytic Dynamic Kinetic Resolution Enabled Asymmetric Synthesis of Phosphorus-Containing Chiral Helicenes

The catalytic asymmetric synthesis of phosphorus-containing helicenes remains a formidable challenge, presumably due to the lack of rational design of substrates, right choice of reactions together with highly effective catalysis systems. Herein, we disclosed an efficient and practical DKR-involving (dynamic kinetic resolution) cascade strategy toward synthesizing a novel family of phosphorus-installing helicenes by peptide-mimic phosphonium salt (PPS) catalysis. The sequential process of PPS-catalyzed phospha-Michael attack and copper salt-facilitated aromatization led to the formation of unprecedented phosphorus-containing oxa[5]helicene scaffolds. A wide variety of substrates bearing an assortment of functional groups were compatible with this protocol, furnishing the expected helical compounds in high yields and excellent stereoselectivities. Additionally, the helical products could be conveniently elaborated to promising phosphine ligands with perfectly retained helical chirality, which turned out to be highly efficient chiral ligands in transition metal-catalyzed reactions. These findings not only expand the current library of phosphorus-containing helicenes but also offer insights to explore other challenging scaffolds with molecular chirality.     

Synthesis of Adenines with a Phosphorus-Containing Group in the 9-Position

Adenine derivatives with a phosphorus-containing substituent on N⁹ have been synthesized, and their structure has been confirmed by ¹H, ¹³C, and ³¹P NMR and IR spectroscopy, X-ray diffraction, MALDI mass spectrometry, and elemental analysis.     

Mechanochemical Synthesis of Short DNA Fragments

We demonstrate the first mechanochemical synthesis of DNA fragments by ball milling, enabling the synthesis of oligomers of controllable sequence and length using multi-step, one-pot reactions, without bulk solvent or the need to isolate intermediates. Mechanochemistry allowed for coupling of phosphoramidite monomers to the 5′-hydroxyl group of nucleosides, iodine/water oxidation of the resulting phosphite triester linkage, and removal of the 5′-dimethoxytrityl (DMTr) protecting group in situ in good yields (up to 60 % over three steps) to produce DNA dimers in a one-pot manner. H-Phosphonate chemistry under milling conditions enabled coupling and protection of the H-phosphonate linkage, as well as removal of the 5′-DMTr protecting group in situ, enabling a one-pot process with good yields (up to 65 % over three steps, or ca. 87 % per step). Sulfurization of the internucleotide linkage was possible using elemental sulfur (S8) or sulfur transfer reagents, yielding the target DNA phosphorothioate dimers in good yield (up to 80 % over two steps). This work opens the door to creation of solvent-free synthesis methodologies for DNA and RNA therapeutics.     

Synthesis and Characterization of New Thiacalix[4]arenes Bearing Semicarbazide and Thiosemicarbazide Fragments at the Lower Rim

Starting from thiacalixarene tetraacetates, tetraacetohydrazides have been prepared and then used for the introduction of semicarbazide and thiosemicarbazide fragments into the lower rim by the reaction with phenyl isocyanate and phenyl isothiocyanate in dry toluene. The structures of the prepared compounds were investigated by FT‐IR, FAB‐MS, ¹H NMR, and X‐ray crystallography, and their receptor properties were examined by liquid liquid extraction of dichromate anions.