An easy access to 2-Amino-5,6-dihydro-3H-pyrimidin-4-one building blocks: The reaction under conventional and microwave conditions

Summary A new one-stage fast multicomponent synthesis of title compounds leads to products in 21–55% isolated yields under both conventional and microwave conditions. The primary amino group in the building blocks can be easily acylated by various usual electophilic agents that can be utilized in the synthesis of diverse heterocylic compounds libraries.     

Solid phase synthesis of allylic alcohols via the Baylis-Hillman reaction

An efficient method for the solid phase synthesis of allylic alcohols via the Baylis-Hillman reaction has been developed. In the presence of DABCO® or 3-quinuclidinol the coupling of resin bound acrylic acid with different aldehydes yields allylic alcohols. Aldehydes with different reactivity were used and gave modest to excellent yields upon simply varying the base or the reaction time. The allylic alcohols were reacted with primary amines to form 1,3-aminoalcohols.     

Alternative method of Boc-removal from sulfamide using silica-phenyl sulfonic acid in conjunction with microwave heating

Summary A general method was used to prepare an array of unsymmetric sulfamides. This was accomplished by the stepwise addition of CSI to tert-butanol followed by the addition of amines. To increase diversity, nitrogen group of Boc-sulfamides was alkylated with alcohols using Mitsunobu reaction and Boc-group was removed using Si-TsOH. Microwave heating was used in all the steps. The final sulfamides were released from Si-TsOH using NH₃ in MeOH.     

Scaffold-directed and traceless synthesis of tricyclic quinoxalinone imidazoles under microwave irradiation

Traceless synthesis of 2-aminoimidazoquinoxalinones has been performed on soluble polymer support under open-vessel microwave dielectric heating. The reaction progression is monitored directly by the conventional proton NMR which indicated no release of the substrate from the support. Fmoc-deprotected amino acid polymer conjugates react with 1,5-difluoro-2,4-dinitro benzene to yield polymer bound dinitro fluoro amines, which are further substituted by various primary amines to yield PEG-immobilized dinitrodiamines. Simultaneous reduction of aromatic meta-dinitro group leads to the traceless release of 2-quinoxalinones, followed by N-hetero cyclization with various isothiocyanates in the presence of mercury(II)chloride to furnish 2-aminoimidazoquinolinone rings with three points of diversity at rapid pace.     

Solid phase synthesis of hydantoins by thermal cyclization and screening of reaction conditions using APOS 1200

A novel strategy for solid-phase synthesis of hydantoins with highoptical purity is described using a thermal pH-neutral cyclization and simultaneous release from resin. Hereby even hydantoins bearinga pH-sensitive side chain (protection) are available. The reaction conditions are well screened applying the parallel organic synthesizerAPOS 1200.     

A reexamination of Biginelli-like multicomponent condensation reaction: One-pot regioselective synthesis of spiro heterobicyclic rings

A pseudo four-component reaction is described, leading to the efficient regioselective synthesis of sigma symmetric spiro heterobicyclic rings using aldehydes and urea in the presence of cyclic beta-diester or beta-diamides such as Meldrum's acid or barbituric acid derivatives. The reaction needs no added catalyst and proceeds solvent-free conditions at 80 degrees C.     

Advances in organic synthesis using polymer-supported reagents and scavengers under microwave irradiation

Summary Microwave-assisted and polymer-supported organic syntheses have emerged independently as versatile tools for rapid generation of organic molecules. Chemists are increasingly looking for a combination of both techniques for efficient organic synthesis. This review covers the recent literature on organic synthesis using microwave heating in conjunction with polymer-supported reagents and scavengers.     

A novel three-component reaction designed by the combinatorial method: Heteroarenes, isothiocyanates and isocyanides

The novel three-component reaction of isoquinoline with isothiocyanates and isocyanides leads to a variety of new imidazoisoquinolines. The zwitterionic ground state of these new ring systems is established by means of NMR and X-ray analysis. Use of phthalazine instead of isoquinoline gives access to imidazole annulated phthalazines.     

Parallel and automated library synthesis of 2-long alkyl chain benzoazoles and azole[4,5-<Emphasis Type="BoldItalic">b</Emphasis>]pyridines under microwave irradiation

Summary A versatile route to 40-membered library of 2-long alkyl chain substituted benzoazoles (1 and 2) and azole[4,5-b]pyridines (3 and 4) via microwave-assisted combinatorial synthesis was developed. The reactions were carried out in both monomode and multimode microwave oven. With the latter, all reactions were performed in high-throughput experimental settings consisting of an 8×5 combinatorial library designed to synthesize 40 compounds. Each step, from the addition of reagents to the recovery of final products, was automated. The microwave-assisted N-long chain alkylation reactions of 2-alkyl-1H-benzimidazole (1) and 2-alkyl-1H-benzimidazole[4,5-b] pyridines (3) were also studied.     

Structure-controllable synthesis of ZnO nanowires using water vapor in an atmospheric-pressure microwave plasma system

Although the use of atmospheric-pressure microwave plasma to synthesize ZnO nanowires addresses various issues associated with conventional synthesis methods, it is difficult to obtain nanowires with controlled diameters and lengths. Herein, we investigated the effects of microwave input power and water vapor on the structure of ZnO nanowires grown using an atmospheric-pressure microwave plasma system. It was found that the aspect ratio of ZnO nanowires could be controlled by adjusting the plasma temperature and the amount of OH radicals. This method successfully produced ZnO nanowires in a structure-controllable manner with a wide range of aspect ratios from 10 to 340. Interestingly, we found that the sensitivity of the ZnO nanowires to UV irradiation was closely related to the morphology. In particular, the ZnO nanowires with high aspect ratios and densities showed excellent sensing characteristics.     

随机相位微波功率的空间合成效率

 采用数值计算方法,将微波功率源输出信号的相位差视为等概率分布的随机事件,通过阵列天线平均增益定量计算了多微波源空间功率合成效率;分析了随机相位条件下,天线单元间耦合系数、极化方式和单元增益对合成效率的影响。计算结果表明：多微波源在随机相位条件下进行空间功率合成,阵列天线单元之间的相互耦合将造成合成效率严重下降;而天线类型、极化方式和天线单元增益对合成效率的影响较小。     

随机相位微波功率的空间合成效率

采用数值计算方法,将微波功率源输出信号的相位差视为等概率分布的随机事件,通过阵列天线平均增益定量计算了多微波源空间功率合成效率;分析了随机相位条件下,天线单元间耦合系数、极化方式和单元增益对合成效率的影响。计算结果表明：多微波源在随机相位条件下进行空间功率合成,阵列天线单元之间的相互耦合将造成合成效率严重下降;而天线类型、极化方式和天线单元增益对合成效率的影响较小。     

Simulation of diesel spray combustion using LES and a multicomponent vapourisation model

Diesel spray and combustion in a constant-volume engine cylinder was simulated by a large eddy simulation (LES) approach coupling with a multicomponent vapourisation (MCV) modelling. The simulation focused on the inclusion of the interaction between fuel spray and gas-phase turbulence flow at the sub-grid scale. The LES was based on the dynamic structure sub-grid model, and an additional source term was added to the filtered momentum equation to account for the effect of drop motion on the gas-phase turbulence. The multicomponent drop vapourisation modelling was based on the continuous thermodynamics approach using a gamma distribution to describe the complex diesel fuel composition and was capable of predicting a more complex drop vapourisation process. The effect of gas-phase turbulence flow on the fuel drop vapourisation process was evaluated through the solution of the gas-phase moments of the distribution in the present LES framework. A non-evaporative spray in a constant-volume engine cylinder was first simulated to examine the behaviours of LES, in comparison with a Reynolds-averaged Navier–Stokes (RANS) simulation based on the RNG k–? model. More realistic diesel spray structures and improved agreement on liquid penetration length with the corresponding experimental data were predicted by the LES, using a grid resolution close to that of RANS. A more comprehensive simulation of diesel spray and combustion in cylindrical combustor was also performed. Predicted distributions of soot particles were compared to the experimental image, and improved agreement with the experimental data was also observed by using the present LES and MCV models. Consequently, results of the present models proved that improved overall performance of the fuel spray simulation can be achieved by the LES without a significant increase in the computational load compared to the RANS.     

Selection of a cyclic nonapeptide inhibitor to α-chymotrypsin using a phage display peptide library

A cyclic nonapeptide library displayed on filamentous bacteriophages was selected 6 times against α-chymotrypsin (EC 3.4.21.1) at three different pH conditions (6.5, 7.0, and 7.5). Phage peptide clones from the sixth selection, at all three pH conditions, interacted more strongly with α-chymotrypsin than the original library and a wild-type phage did. DNA sequencing of the selected phage peptide clones showed that different cyclic nonapeptide sequences had been selected at the different pH conditions. The oxidized form of the synthetic peptide, Cys-Cys-Phe-Ser-Trp-Arg-Cys-Arg-Cys, selected at pH 7.5, could completely inhibit the enzymatic activity of α-chymotrypsin. The structurally related enzymes trypsin (bovine) and elastase (porcine) were only marginally inhibited by the same peptide under the same conditions. The inhibition constant for α-chymotrypsin was estimated to be 10^-6 M. Phage clones expressing this peptide had a lower affinity for phenylmethylsulfonylfluoride-modified α-chymotrypsin than for natural α-chymotrypsin as determined by an enzyme immunosorbent assay. This peptide phage clone was also competitively prevented from binding to α-chymotrypsin by the corresponding synthetic oxidized peptide. Collectively, the results suggest that the oxidized form of the selected peptide Cys-Cys-Phe-Ser-Trp-Arg-Cys-Arg-Cys interacts with the active site of α-chymotrypsin and acts as a specific inhibitor to the enzyme. To our knowledge, the selected sequence Cys-Cys-Phe-Ser-Trp-Arg-Cys-Arg-Cys has not been found in nature. This revised version was published online in August 2006 with corrections to the Cover Date.     

Six new photolabile linkers for solid-phase synthesis. 1. Methods of preparation

In the synthesis of combinatorial chemical libraries on solid phase, there is a need to cleave the compounds from the solid support before the library can be tested for biological activity. It is advantageous to use linkers which will release the libraries by mild photolytic cleavage. We have developed six new linkers of the photosensitive α-methyl 2-nitrobenzyl type containing amino, hydroxy, bromo and methylamino groups, and also 4-nitrophenoxycarbonyl activated OH and NH₂ groups. This revised version was published online in August 2006 with corrections to the Cover Date.     

1H NMR spectroscopy with internal and external standards for the quantification of libraries

A convenient and easy method based on 1H NMR spectroscopy with both external and internal standards is described for the quantification of members of libraries.     

Six new photolabile linkers for solid phase synthesis. 2. Coupling of various building blocks and photolytic cleavage

Photolabile linkers are very useful in the generation of combinatorial libraries as they offer compound cleavage under mild conditions directly into a solvent suitable for biological testing. Six new photolabile linkers have been developed which allow coupling of building blocks with a carboxy, amino, hydroxy and sulfonyl group. Photolytic cleavage of these building blocks will give libraries with carboxy, amido, methylamido, amino, ureido, hydroxy, aminocarbonyloxy and aminosulfonyl terminal groups. Coupling conditions for these reactions were elucidated and the photolytic cleavage reaction was studied.     

Rapid synthesis and characterization of silicon substituted nano hydroxyapatite using microwave irradiation

Nano sized hydroxyapatites with silicon substitution of three different silicon concentrations were successfully prepared first time by a rapid microwave assisted synthesis method, with a time saving and energy efficient technique. The effects of the Si substitution on crystallite size, particle size and morphology of the powders were investigated. The crystalline phase, microstructure, chemical composition, and morphology and particle size of hydroxyapatite and silicon substituted hydroxyapatites were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and dynamic light scattering. The crystallite size and particle size decreases with increase in silicon content and particle morphology spheroidal for pure hydroxyapatite changes to elongated ellipsoidal crystals while silicon substitution increases. Fourier Transform Infrared Spectroscopy analysis reveals, the silicon incorporation to hydroxyapatite lattice occurs via substitution of silicate groups for phosphate groups. Substitution of phosphate group by silicate in the apatite structure results in a small increase in the lattice parameters in both a-axis and c-axis of the unit cell.     

Solid phase synthesis of combinatorial libraries using anhydrides as templates

A simple and general approach to the synthesis of chemical libraries based on a universal anhydride template allows the preparation of large number of compounds. Various cyclic/acyclic amines, primary/secondary amines, differentially protected bifunctional amines were used as nucleophiles to react with anhydrides. The free carboxylic acid generated was then coupled with solid-bound amines. The facile and rapid generation of compounds through this multi-component assembly can be accomplished in a combinatorial parallel synthesis. This revised version was published online in August 2006 with corrections to the Cover Date.     

High Throughput Analysis and Purification in Support of Automated Parallel Synthesis

Rapid reverse-phase analytical and preparative HPLC methods havebeen developed for application to parallel synthesis libraries.Gradient methods, short columns, and high flow rates allowanalysis of over 300 compounds per day on a single system, orpurification of up to 200 compounds per day on a singlepreparative system. Hardware and software modifications allowcontinuous unattended use for maximum efficiency and throughput.