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.     

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.     

On the role of the colloidal stability of mesoporous silica nanoparticles as gene delivery vectors

Mesoporous silica nanoparticles have been synthesized and functionalized with four different types of molecules containing amino groups, i.e., with primary amines only, with quaternary amines, with quaternized cyclic amines, or with polyethylenimine (PEI), which is formed by primary, secondary, and tertiary amines. These nanoparticles were then incubated with reporter plasmids and the ability of the resulting complexes to transfect human cells was studied. Only nanoparticles functionalized with PEI were efficient for transfection. The agglomeration behavior and the electrokinetic potential of the nanoparticle–plasmid complexes have been studied, as well as their cell internalization behavior using a fluorescent-labeled plasmid that allows its monitorization by confocal microscopy. The results indicate that the efficiency of PEI-functionalized nanoparticles for transfection resides to some extent in the different characteristics imparted to the nanoparticles regarding agglomeration and surface charge behavior.     

Solution-phase reductive cyclization of 2-quinoxalinol analogs: Systematic study of parallel synthesis

1,5-Difluoro-2,4-dinitrobenzene starting material was treated via primary and/or secondary substitution with a variety of amino acids or amines and the aromatic m-dinitro groups were then reductively cyclized provide the 2-quinoxalinol analogs. The conditions for 1,5-dialkylamino-2,4-dinitrobenzene reduction have been systematically studied and optimized in solution. Three effective methods are described for the high-throughout generation of 2-quinoxalinol analogs.     

芳胺-二苯酮光化夺氢反应活泼自由基的ESR研究

本文用自由基捕捉剂与ESR相结合的方法系统研究了各种取代苯胺与二苯酮光化夺氢反应中的活泼自由基。找出了形成N-中心及C-中心自由基的条件:即当芳胺有N上氢和α-C上氢时,优先形成N-中心自由基;仅当无N上氢时,才形成C-中心自由基。     

Ionic liquid-supported synthesis of dihydroquinazolines and tetrahydroquinazolines under microwave irradiation

An efficient microwave-assisted and water-soluble ionic liquid (IL)-supported synthesis of medicinally important dihydro- and tetrahydroquinazolines has been developed. The protocol involves the S(N)2 substitution reaction of IL-bound 4-bromomethyl-3-nitrobenzoic acid with various primary amines to provide IL-bound 4-((alkylamino) methyl)-3-nitrobenzoate under microwave irradiation. Further elaboration followed by sequential cyclization with various isothiocyanates and aldehydes furnished IL-bound target compounds. Cleavage of the IL support by methanolysis gave dihydro- and tetrahydroquinazolines with high purity and excellent yields. The new protocol has the advantages of shorter reaction time, easy workup process, excellent yields, reduced environmental impact, wide substrate scope, and convenient procedure.     

Mass Spectrometric Investigation of Some Pyronylpyrazole Derivatives

The electron impact ionization mass spectra of some pyronylpyrazoles were investigated. The 6-substituted 4-hydroxy-2-pyrone ring in all compounds fragments according to the common mechanisms. The fragmentations of the 3,5-disubstituted N-phenylpyrazole moiety are strongly dependent on the nature and positions of the substituents.     

胺对联苯胺黄颜料的电荷控制作用及其红外光谱分析

为了确定胺类化合物,特别是聚异丁烯琥珀酰氨(PIBI)对联苯胺黄颜料颗粒的电荷控制作用,选择一系列氨基化合物与联苯胺黄PY14反应,同时进行四乙五胺成盐实验,通过测试产物的Zeta电位和红外光谱,对比分析电荷控制机理,还根据Zeta电位值,研究了不同取代氨对PY14的电荷控制作用强弱。根据氨基和成盐氨基的红外吸收频率,确认胺对PY14的电荷控制作用主要是Lewis酸碱反应,空间位阻小的仲胺和伯胺的电荷控制作用比较强,发现PY14 Zeta 电位值发生反号,是由于大的反号离子在颜料表面吸附所致。     

The SIMS spectrum of the O-W(100) chemisorption system

The adsorption of oxygen on clean W(100) has been studied with static mode SIMS. Studies were made at different temperatures and oxygen exposures under stringent vacuum conditions. Both the positive and negative secondary ion spectra were investigated by using low energy (500 eV) and low current density Ne⁺ primary ions, so that the adsorbed layer was not perturbed. The correlations among the secondary ions O⁺, O^? and various tungsten oxide ions showed qualitative changes at different stages of chemisorption. All these features corresponded very well to the structural and adsorption site changes observed with LEED and other techniques. This work shows that SIMS can give structural and chemical information of chemisorbed layers in the submonolayer range.     

Fluorous parallel synthesis of a hydantoin/thiohydantoin library

Fluorous tagging strategy is applied to solution-phase parallel synthesis of a library containing hydantoin and thiohydantoin analogs. Two perfluoroalkyl (Rf)-tagged -amino esters each react with six aromatic aldehydes under reductive amination conditions. Twelve amino esters then each react with 10 isocyanates and isothiocyanates in parallel. The resulting 120 ureas and thioureas undergo spontaneous cyclization to form the corresponding hydantoins and thiohydantoins. The intermediate and final product purifications are performed with solid-phase extraction (SPE) over FluoroFlash^TM cartridges, no chromatography is required. Using standard instruments and straightforward SPE technique, one chemist accomplished the 120-member library synthesis in less than five working days, including starting material synthesis and product analysis.     

Fukuyama reduction,Fukuyama coupling and Fukuyama–Mitsunobu alkylation: recent developments and synthetic applications

Fukuyama reaction for the synthesis of multifunctional aldehydes, secondary amines and ketones has gained considerable importance in synthetic organic chemistry because of mild reaction conditions. The use of thioesters in both Fukuyama aldehydes and ketones synthesis is highly attractive for organic chemists as they are easily accessible from corresponding carboxylic acids. Fukuyama–Mitsunobu reaction utilizes 2-nitrobenzenesulfonyl (Ns) for the protection/activation/deprotection of primary amines to afford secondary amines in good yields and high enantioselectivities. This review presents recent synthetic developments and applications of Fukuyama reaction for the synthesis of aldehydes, secondary amines and ketones.

Graphic abstract

     

Multiple solid-phase synthesis of hydantoins and thiohydantoins

A novel general protocol for the construction of hydantoins and thiohydantoins on a solid support has been developed. Using this novel methodology, the synthesis of a diverse 96-compound library has been achieved. Resin-bound dipeptides are cyclised via the formation of an intermediate isocyanate or isothiocyanate on resin as the key step in the strategy. This revised version was published online in August 2006 with corrections to the Cover Date.     

Regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine on solid support

An efficient solid phase regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine template exemplified by 4-H-2,3,4,5-tetrahydro-7-iodo-3-oxo-1H-1,4-benzodiazepine-2-acetate-polymerester is described. Further chemical elaboration atposition 7, utilizing a modified Heck reaction, allows the incorporationof amides from primary or secondary amines. The two diversity points atpositions 4 and 7 were utilized tosynthesize a 28-membered, combinatorial array on Sasrin® resin in moderate yields and >80% purity. Having validated the chemistry on solid support, acombine and splitapproach to prepare a bead-bound combinatorial library is achievableutilizing similar experimental practices and procedures as in thearray synthesis.     

Synergistic effect of dual-frequency ultrasound irradiation in the one-pot synthesis of 3,5-disubstituted isoxazoles

Herein is reported a one-pot three-step process for the regioselective synthesis of 3,5-disubstituted isoxazoles based on copper(I)-catalyzed cycloaddition reaction between in situ generated nitrile oxides (from the corresponding aldehydes) and alkynes, using ultrasound irradiation, avoiding toxic reagents and solvents and isolation/purification of intermediates.The combined use of 40 kHz ultrasonic bath and 20 kHz probe in the presence of copper turnings reduced reaction time to 1 h and resulted in only one final purification step with increased yields, clearly indicating that there is a dual-frequency synergistic effect.In addition, under metal free conditions, the 1,3-dipolar cycloaddition was regioselective giving low to modest yields.     

Ultrasound-promoted access to Baylis–Hillman amines

It is surveyed that the amination of the Baylis–Hillman acetates with primary amines can be dramatically promoted in improved yields and shortened reaction time under ultrasound irradiation than those under conventional stirring. The extensive scope of both amines and acetates are screened to investigate the relationship between substituents and their performance in such transformation.     

苯并呋咱-1-氧化物与二级胺光化学反应的电子自旋共振研究

本文报道了二苯胺、甲基苯基胺、甲潜苄胺、二苄胺、二异丙胺和二乙胺分别与苯并呋咱-1-氧化物在紫外光照下发生光化学反应的电子自旋共振(ESR)研究结果。结果表明:紫外光的作用首先使苯并呋咱-1-氧化物处于激发态,它与二胺作用生成激基态络合物,经氧转移和二胺的氮氢键断裂而最终生成相应的氮氧自由基。     

A simple approach to the synthesis of highly functionalized 3-alkylidene-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-ol derivatives and related pyrroles

The reaction of various primary amines with acetylenic esters at ambient temperature in THF/H₂O (50:50) produced related enaminones. Subsequently reaction of these in situ prepared enaminones with dibenzoylacetylene leads to 3-alkylidene-2,3-dihydro-1H-pyrrol-2-ol derivatives in good yields. The reaction of these products with various alcohols in the presence of a catalytic amount of HCl produced highly functionalized pyrroles in nearly quantitative yields.     

Quantifying amino acid and protein substitution using Raman spectroscopy

Raman spectroscopy can be a powerful tool for the characterization of modified amino acids and proteins. In addition to the potential for quantitative results, it offers the advantage of not requiring any sample preparation. Modification of amines and thiols on amino acids and proteins are common reactions used for medical, biological, food, and agricultural purposes. We hypothesized that the Raman spectrum could be used to quantify the reactions and would be more informative than typical characterization techniques such as the ninhydrin test. To prove the hypothesis, the amino acids alanine, cysteine, and lysine were modified with ethyl vinyl sulfone (EVS) using a nucleophilic addition reaction known as the Michael addition and the product was characterized using Raman spectroscopy. The Raman spectroscopy results were compared with ultraviolet‐visible spectroscopy results based on ninhydrin analysis of the modified amino acids. The Raman spectroscopy analysis was able to discern site‐specific reactions on the amino acids and suggested that more amino acid moieties were substituted than predicted using the ninhydrin test alone. Substitution of the full protein ovalbumin with EVS showed similar results. The ninhydrin test showed the substitution of primary amines and thiols but could not detect substitution of secondary amines remaining after loss of the primary amine. Copyright © 2010 John Wiley & Sons, Ltd.     

Preparation of N-alkylated 5-oxo-3-carboxamyl-1,4-thiazinanes on solid support

A general method was developed to generate six-membered cyclic thiazinanes on solid support. Three diversity sites were introduced into this scaffold using primary amines, aldehydes, and 2-bromoalkanoic acids. The methodology to prepare individual cyclic thiazinanes as well as combinatorial libraries of these compounds is described.     

First ultrasound-mediated one-pot synthesis of N-substituted amides

Ultrasound irradiation, an efficient and innocuous technique of reagent activation for synthesizing organic compounds, has been applied with success to transform seven carboxylic acids to fourteen secondary amides in good to excellent yields. The reaction has worked well either with aryl or alkyl carboxylic acids as well as with aromatic or aliphatic amines. This methodology is expeditious and reliable for preparing secondary carboxamides which in many cases are embedded in the C-5 side-chain of 1,2,4-oxadiazoles (14, 15, 17–27). The elemental analyses of new compounds (19–27) in conjunction with the spectral data of all synthesized amides gave an idea about their structures, while the crystallographic data of one of the compounds (26) supplied information concerning the configurational behavior of the amidic part and also the conformational aspect of the entire molecule in the crystalline state.