Abed Al Aziz Quntar

Natural and synthetic small boron-containing molecules as potential inhibitors of bacterial and fungal quorum sensing.

Chemical communication is a phenomenon exhibited by many different organisms and nowadays is one of the most prominent research areas at the chemistry-microbiology interface.1–6 For more than 20 years, science has recognized the ability of different bacteria to coordinate phenotype expression using signaling substances, which is a crucial process for successful environment colonization in plants, other animal hosts, and also for human beings7–10

Synthesis and evaluation of thiazolidinedione and dioxazaborocane analogues as inhibitors of AI-2 quorum sensing in Vibrio harveyi.

Two focused libraries based on two types of compounds, that is, thiazolidinediones and dioxazaborocanes were designed. Structural resemblances can be found between thiazolidinediones and well-known furanone type quorum sensing (QS) inhibitors such as N-acylaminofuranones, and/or acyl-homoserine lactone signaling molecules, while dioxazaborocanes structurally resemble previously reported oxazaborolidine derivatives which antagonized autoinducer 2 (AI-2) binding to its receptor. Because of this, we hypothesized that these compounds could affect AI-2 QS in Vibrio harveyi. Although all compounds blocked QS, the thiazolidinediones were the most active AI-2 QS inhibitors, with EC(50) values in the low micromolar range. Their mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of V. harveyi QS mutants and by DNA-binding assays with purified LuxR protein. The active compounds neither affected bioluminescence as such nor the production of AI-2. Instead, our results indicate that the thiazolidinediones blocked AI-2 QS in V. harveyi by decreasing the DNA-binding ability of LuxR. In addition, several dioxazaborocanes were found to block AI-2 QS by targeting LuxPQ.

Recent Advances in the Medicinal Chemistry of α-Aminoboronic Acids, Amine-Carboxyboranes and Their Derivatives

This article describes recent developments in the synthesis and biological activity of alpha-aminoboronic acids, amine-carboxyboranes and their derivatives as potential therapeutic agents. alpha-Amino acid analogues are of considerable interest as inhibitors of enzymes involved in amino acid and peptide metabolism. In particular, alpha-amino alkylphosphonic acids and alpha-amino alkylboronic acids, in which the carboxyl group of amino acids is replaced by a phosphonic acid or boronic acid function, respectively, constitute a unique class of amino acid mimics from which a number of potent enzyme inhibitors have been synthesized. The inhibitory activity mainly stems from the fact that the tetrahedral phosphonic moiety or the tetrahedral adduct of electrophilic boronic acid is a good mimic of the putative tetrahedral transition state or intermediate encountered in the enzymatic hydrolysis or formation of peptides. Since the peptide hydrolysis and formation invariably involves the tetrahedral high energy species in the course of the reaction, these amino acid mimics serve as a general key element for inhibitors of a broad spectrum of proteases and peptide ligases. Serine protease inhibitors provide promising compounds having a P site binding moiety and a boronic acid chelating moiety. The compounds have been shown to have high inhibitory activity.

Novel addition reactions of titanacycle phosphonates by tuning of Ti(O-i-Pr)4/2i-PrMgClElectronic supplementary information (ESI): further experimental details. See http://www.rsc.org/suppdata/cc/b2/b209149f/

Di- or tri-substituted vinylphosphonates, 2-5, can be obtained in a highly regio- and stereoselective manner from 1-alkynylphosphonates, by manipulation of Ti(O-i-Pr)4/2i-PrMgCl.

Propargylic sulfides: synthesis, properties, and application.

Svetlana A. Vizer,† Elena S. Sycheva,† Abed Al Aziz Al Quntar,‡ Nurzhan B. Kurmankulov,† Kazbek B. Yerzhanov,† and Valery M. Dembitsky* †A.B. Bekturov Institute of Chemical Sciences, 106 Sh. Walikhanov Street, Almaty 480100, Republic of Kazakhstan ‡Department of Material Engineering, Faculty of Engineering, Al Quds University, Abu Deis 51000, Palestine Institute of Drug Discovery, P.O. Box 45289, Jerusalem 91451, Israel

Isomerization of diethyl 1-alkynylphosphonates to 1,3-dienylphosphonates followed by Diels-Alder reaction with dead, maleic anhydride and maleimide

† Dedicated to Prof. Dr. Albert Eschenmoser on occasion of his 85th birthday. Abstract - Isomerization of diethyl 1-alkynylphosphonates, 1, with Pd((PPh)3)4 in refluxing 1,4-dioxane provides 1,3-dienylphosphonates, 2, in satisfactory to excellent isolated yield (45-83%). The reaction is tolerant of chlorides and cyclic substituents. Cycloaddition reaction of 2 with DEAD provided the corresponding diethyl 3-(diethoxyphosphoryl)-6-alkyl-3,6-dihydropyridazine- 1,2-dicarboxylates, 3, in 85% isolated yield. The cycloaddition products can be obtained in a one-pot reaction directly from the isomerized 1-alkynylphosphonates with no loss in yields. Similarly, 1,3-dioxo-1,3,3a,4,7,7a- hexahydroisobenzofuran-4-ylphosphonate, and 1,3-dioxo-2,3,3a,4,7,7a- hexahydro-1H-isoindol-4-ylphosphonate 4 were obtained by reacting 1,3-dienylphosphonates with maleic anhydride and maleimide respectively.

PINACOLBORATAMETHYL- ENETRIPHENYLPHOSPHONIUM IODIDE, A NEW METHYLENE TRANSFER REAGENT

ABSTRACT The title compound is easily prepared and reacts with various aldehydes and ketone. The reagent is compatible with free hydroxy groups. Yields with various aldehydes and ketones are in 50–>99% range. Both aliphatic, aromatic and unsaturated carbonyls react.

Novel 3-hydroxy vinylboronates influence sphingolipid metabolism, cause apoptosis in Jurkat cells and prevent tumor development in nude mice

A series of novel 3-hydroxy vinylboronates which share structural similarities with sphingolipids were synthesized and tested in vitro and in vivo as anticancer agents. The molecules reduced cancer cell survival in vitro by influencing their sphingolipid metabolism. In a cancer model in nude mice the lead compound E7 prevented the development of tumor as long as the treatment period continued. Moreover, it delayed tumor growth after the treatment was finished.