Bivalent Organophosphorus Compounds—Synthesis and Acetylcholinesterase Inhibitory Activity

Abstract

A series of novel symmetric S,S′-2,2′-(ethane-1,2-diylbis(azanediyl)) bis(2-oxoethane-2,1-diyl) O,O,O′,O′-tetraethyl diphosphorodithioate derivatives (12) was designed and synthesized based on the cluster effect and the multiple binding sites of acetylcholinesterase (AChE). The structures of all the newly synthesized title compounds were characterized by ¹ Choi, S. K. Synthetic Multivalent Molecules: Concepts and Biomedical Application, 20–21. New Jersey: John Wiley & Sons, Inc. 2004, chapter 1 [Google Scholar]H and ¹³ Tang, H., Zhao, L. Z., Zhao, H. T., Huang, S. L., Zhong, S. M., Qin, J. K., Chen, Z. F., Huang, Z. S. and Liang, H. 2011. Euro. J. Med. Chem., 46: 4970–4979. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]C NMR as well as elemental analyses. Their inhibitory activities against AChE were tested, and compound 12b exhibited the best activity (6.60-fold higher than ethion). The results suggested that the compound would bind to the catalytic center and the narrow gorge of the AChE simultaneously.

Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional table.     

The Investigation of Interaction Competition Between ATP and DIPP-Ala,Boc-Ala,or Ala by ESI-MS/MS and Theoretical Calculation

The interactions between ATP and N-(O,O-diisopropyl) phosphoryl-L-alanine (DIPP-Ala), N-(tert-butoxycarbonyl)-L-alanine (Boc-Ala), or L-alanine (Ala) were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The non-covalent complexes between ATP and Boc-Ala or DIPP-Ala were observed, while the complex between ATP and Ala was not found in the mass spectra. The affinity of DIPP-Ala for ATP was confirmed to be stronger than that of Boc-Ala by competition experiment. Through molecular modeling calculations, it was found that the non-covalent complexes were stabilized by intermolecular hydrogen bonds, and the affinity sequence for ATP was DIPP-Ala > Boc-Ala > Ala by comparing their binding energy, ?35.407 kcal/mol, ?15.634 kcal/mol, ?6.555 kcal/mol, respectively. The results implied that a phosphoryl group was a very important functional group to provide an interaction site between amino acids and ATP, and that N-phosphoryl amino acids can be used as a good model of protein in the studies of molecular recognition of ATP.     

Solid-Phase Synthesis of 2-Arylamino-5-(4-hydroxyphenyl)-1,3,4-thiadiazole Derivatives Based on Resin-Bound Acylhydrazines

A highly efficient, solid-phase synthesis of 2-arylamino-5-(4-hydroxy-phenyl)-1,3,4-thiadiazole derivatives under mild conditions has been developed. The 1,3,4-thiadiazole derivatives were synthesized from resin-bound acylhydrazines in several steps, which gave 78–88% overall yields and excellent purities of the products.     

The Synthesis and 31P NMR Spectral Studies of Cyclophosphazenes

A modified method for preparing large-scale quantities of pure hexachlorocyclophosphazene (N₃P₃Cl₆) and octachlorocyclotetraphosphazene (N₄P₄Cl₈), phosphorus pentachloride with ammonium chloride, in the presence of zinc chloride, has been developed. The time of the reaction and the quantities of the catalyst are also studied. It is found that the optimum reaction time is 1.5 h and by-products are remarkably reduced by addition of 10% zinc chloride. As indicated by the ³¹ P NMR spectra, the synthesis and separation of cyclophosphazenes can be accomplished in moderate yield of tetramer (39%) and good yield of trimer (83%).     

The Synthesis of Amino Acid Methyl Ester 5′-Phosphoamidates of Protected Uridine

In this article, we used the Atherton–Todd reaction to synthesize amino acid methyl ester 5′-phosphoamidates of uridine as prodrugs. Their structures were confirmed by ¹H NMR, ³¹P NMR, ¹³C NMR, IR, and mass spectrometry.

Supplemental materials are available for this article. Go to the publisher′s online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Recognition of α-Amino Acid from β- and γ-Amino Acid by N -Phosphorylation

The reactivity of N -phosphoryl f -alanine differs from N -phosphoryl g -alanine and N -phosphoryl n -amino butyric acid enormously. N -phospho- f -alanine could self-activate to yield N -phosphopeptides either in aqueous or nonaqueous media, but not g - or n -amino acid analogues. The mechanism of the reaction is discussed.     

Synthesis and Characterization of Nitrogen Heterocyclic Derivatives Containing Sulfur–Ether and Schiff Base

Abstract

A series of new nitrogen heterocyclic compounds containing sulfur–ether (8a–8f) and Schiff-base (9a–9q) functionalities were synthesized by the reaction of the pharmaceutical lead compound containing both benzimidazole and 1,2,4-triazole rings. The compounds were characterized by ¹H NMR, ¹³C NMR, FT-IR, HR-MS, and ESI-MS.     

Phenol-formaldehyde resin route to the synthesis of several iron group transition metal phosphides

Abstract

A series of iron, cobalt and nickel metal phosphides of chemical formula Fe_xP, Co₂P and Ni₂P with high specific surface areas of 331.1, 294.2 and 228.0 m² g^?1, respectively, was firstly synthesized by phenol-formaldehyde resin route. It was found that the as-prepared Co₂P and Ni₂P samples synthesized using phenol-formaldehyde resin as a carbon source showed much higher BET surface areas than those prepared using other carbon sources reported before, including cinnamic strong alkali anion exchange resin, p-phenylenediamine and hexamethylenetetramine. This phenol-formaldehyde resin route was proved to be as universal as traditional H₂ reduction method.     

Synthesis,polymerization, and thermal properties of benzoxazine based on bisphenol‐S and allylamine

A bifunctional benzoxazine monomer, 6,6′‐bis(3‐allyl‐3,4‐dihydro‐2H‐benzo[e][1,3]oxazinyl) sulfone (BS‐ala), was synthesized from bisphenol‐S, allylamine and formaldehyde via a solution method. The chemical structure of BS‐ala was confirmed by ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and elemental analysis. The polymerization behavior of BS‐ala was investigated by FTIR, solid‐state ¹³C NMR, and differential scanning calorimetry (DSC). The oxazine ring opening polymerization is prior to the addition polymerization of allyl group, and the exothermic peaks corresponding to the two reactions appear partially overlapped in the DSC curve. The storage modulus of the resultant polybenzoxazine at 25°C is about 3.9 GPa, and the glass transition temperature is 254°C. The 5% and 10% weight loss temperatures of the polybenzoxazine are about 335°C and 361°C in both air and nitrogen, respectively. The char yield is about 58% at 800°C in nitrogen, whereas almost no residue is remained at 700°C in air. Copyright © 2012 John Wiley & Sons, Ltd.     

Dissociations of Complexes Between Monovalent Metal Ions and Aromatic Amino Acid or Histidine

The fragmentations of [AA + M]⁺ complexes, where AA = Phe, Tyr, Trp, or His, and M is a monovalent metal (Li, Na, or Ag), have been exhaustively studied through collision-induced dissociation (CID) and through deuterium labeling. Dissociations of the Li- and Ag-containing complexes gave a large number of fragment ions; by contrast, the sodium/amino acid complexes have lower binding energies, and dissociation resulted in much simpler spectra, with loss of the entire ligand dominating. Unambiguous assignments of these fragment ions were made and formation mechanisms are proposed. Of particular interest are fragmentations in which the charge was retained on the organic fragment and the metal was lost, either as a metal hydride (AgH) or hydroxide (LiOH) or as the silver atom (Ag^?).