A simple copper-catalyzed synthesis of tertiary acyclic amides

The N-arylation of aromatic and aliphatic secondary acyclic amides, known to be poor nucleophiles, has been accomplished using a simple and cheap copper catalytic system. The corresponding tertiary acyclic amides, which can be found in numerous biologically active compounds, have been obtained in good to excellent yields.     

Rational Design to Construct Pyridinonethiol and Its Annulated Frameworks of Expected Significant Antitumor Activity and Geometrical Optimizations

We exploited the utilization of 2‐methyl‐2‐phenyl‐1,3‐oxathiolan‐5‐one ( 1 ) that acts as activated thioglycolic acid as mercaptoacetyl transfer agent to build new pyridinonethiol derivatives via multicomponent domino reactions of 1 with different acyclic or cyclic α ,β‐unsaturated carbonyl compounds and aniline using CeCl₃∙7H₂O/KI as Lewis acid catalyst. Furthermore, the new synthesized compounds were biologically evaluated for antitumor efficiency. The geometries and normal modes of vibrations obtained from calculations are in good agreement with the experimentally observed data.     

Fast atom bombardment mass spectrometry; a promising tool for structural studies

Fast atom bombardment mass spectrometry (FABMS) is a powerful new structural tool. Ionization is effected by bombarding a glycerol matrix with neon or argon atoms of 5–10 KeV energy. Positive and negative secondary ions are sputtered from the surface and can be detected for inorganic ion clusters to mass 25 800 and biologically important compounds to mass 5 700. FABMS is especially valuable in determining the sequence of amino acids in polypeptides.     

Determination of acid-base dissociation constants of amino- and guanidinopurine nucleotide analogs and related compounds by capillary zone electrophoresis

CZE has been applied for determination of acid-base dissociation constants (pKa) of ionogenic groups of newly synthesized amino- and (amino)guanidinopurine nucleotide analogs, such as acyclic nucleoside phosphonate, acyclic nucleoside phosphonate diesters and other related compounds. These compounds bear characteristic pharmacophores contained in various important biologically active substances, such as cytostatics and antivirals. The pKa values of ionogenic groups of the above compounds were determined by nonlinear regression analysis of the experimentally measured pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by CZE performed in series of BGEs in a broad pH range (3.50-11.25), at constant ionic strength (25 mM) and temperature (25 degrees C). pKa values were determined for the protonated guanidinyl group in (amino)guanidino 9-alkylpurines and in (amino)guanidinopurine nucleotide analogs, such as acyclic nucleoside phosphonates and acyclic nucleoside phosphonate diesters, for phosphonic acid to the second dissociation degree (-2) in acyclic nucleoside phosphonates of amino and (amino)guanidino 9-alkylpurines, and for protonated nitrogen in position 1 (N1) of purine moiety in acyclic nucleoside phosphonates of amino 9-alkylpurines. Thermodynamic pKa of protonated guanidinyl group was estimated to be in the range of 7.75-10.32, pKa of phosphonic acid to the second dissociation degree achieved values of 6.64-7.46, and pKa of protonated nitrogen in position 1 of purine was in the range of 4.13-4.89, depending on the structure of the analyzed compounds.     

Recent applications of ring-closing metathesis in the synthesis of lactams and macrolactams

Lactams are an important class of compounds owing to their presence in numerous biologically active molecules of natural and unnatural nature. They are also highly versatile intermediates that can be elaborated into interesting compounds for potential use in organic and medicinal chemistry endeavors. In this feature article, the reader will be given a background to olefin metathesis followed by concise discussions (with selected examples) to report recent applications of ring-closing metathesis to form lactams and macrolactams from acyclic diene precursors, an area which continues to deposit attractive applications in the chemical literature en route or in the final step to the target molecules.     

二烯丙基硫醚化合物的合成

二烯丙基一硫醚（DS）,二烯丙基二硫醚（DDS）,二烯丙基三硫醚（DTS）和二烯丙基四硫醚（DTTS）等是大蒜提取液中的主要有效成分,具有十分广泛独特的生理药理活性。作者以甲酸、丙三醇为超始原料合成了这些化合物,烯丙基硫醚化合物总含量达83%,其中DDS,DTS含量分别达30%。产物均GC-MS鉴定确证。合成方法简单,原料易得,反应步骤少,实用性较强。     

Determination of Glycerol and Serum Triglycerides with Collagen-Immobilized Glycerol Dehydrogenase and Amperometric Detection

Abstract

An amperometric procedure is described for the determination of glycerol and triglycerides in aqueous samples and in serum using glycerol dehydrogenase immobilized on a collagen membrane. Glycerol is determined by measurement of the steady-state oxidation currents generated at a platinum electrode by NADH produced in the enzyme-catalyzed reaction. The triglycerides were first hydrolyzed by the enzyme lipase in solution and the resulting glycerol determined similarly. Olive oil, determined to contain 78 % triolein, was used as the source of triglycerides in this study. For both glycerol and triglycerides the calibration plots are linear in the range from 0 to 12 μM, with detection limits of 0.2 and 0.7 μM, respectively. The immobilized glycerol dehydrogenase retained high operational activity for a period longer than 30 days.     

Triglyceride Assay by Amperometric Microbial Biosensor: Sample Hydrolysis and Kinetic Approach

ABSTRACT

A triglyceride assay based on triglyceride hydrolysis and glycerol detection was developed. Non-specific lipase isolated from Candida rugosa and intact Gluconobacter oxydans cells, containing membrane-bound glycerol dehydrogenase, were used to develop a biosensor. Two approaches were investigated: analysis of pre-hydrolysed samples and a kinetic approach. The sensor prepared from G. oxydans cells exhibited sensitive and fast response to glycerol: detection limit 20 μM (S/N=3), linear range up to 2 mM and response time 84 s (90% of steady-state). The triglyceride assay of pre-hydrolysed samples was based on a 20 min hydrolysis and determination of released glycerol by the biosensor. A calibration curve linear up to 12 mM was obtained for triolein samples. The kinetic approach was based on simultaneous glyceride hydrolysis and glycerol detection. Analysis time of 10 min, linear range up to 30 mM, and estimated detection limit of 50 μM were achieved using the kinetic approach. The kinetic triglyceride assay is not influenced by free glycerol present in a sample. Storage stability, expressed as a half life (50% of the initial response), was 7 days when trehalose was used as a stabiliser.     

Fluorescent cyclodextrins as chemosensors for the detection of cyclic and acyclic alcohols

Molecular sensing abilities and selectivities of a “turn-on” chemosensor, NBDamine-appended α-cyclodextrin (NC0αCD), were studied for cyclic alcohols and acyclic alcohols. This chemosensor is more sensitive to cyclic alcohols than acyclic alcohols, although its binding affinity is stronger for acyclic alcohols than cyclic alcohols.     

Recent advances in the iron-catalysed multicomponent reactions

Iron-catalysed reactions are widely used in organic synthesis owing to its benefits over other metals. Among the important organic reactions, multicomponent reactions play a significant role due to its greener aspects like high atom economy, minimal amount of by-product, economic feasibility etc. For the past few years, iron-catalysed multicomponent reactions have attracted the attention of several chemists which lead to the invention of some fine chemistry. The majority of iron-catalysed multicomponent reactions results in the synthesis of heterocyclic compounds having biologically active natural products, pharmaceutical etc. These developments in the iron-catalysed multicomponent reactions are the focus of this review. This is the first review in this topic which covers the literature up to 2020, and it encompasses the different methods for the synthesis of acyclic, carbocyclic and heterocyclic compounds.     

Oxime-based methods for synthesis of stereodefined acyclic polyfunctionalized δ-azido-nitriles and 5-substituted isoxazoles from carbohydrate derivatives

Hydroxylamine-mediated syntheses of stereodefined acyclic polyfunctionalized δ-azido-nitriles and 5-substituted isoxazoles, bearing a differentially protected glycerol moiety, from 2-deoxysugars and glycals are described.     

Transition metal-catalyzed asymmetric reactions using P-chirogenic diaminophosphine oxides: DIAPHOXs

This review describes the development of a new class of chiral phosphorus ligands: amino acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation with cyclic beta-keto esters as prochiral nucleophiles was initially examined using P-chirogenic diaminophosphine oxide 1a, resulting in highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 13, which functions as the actual ligand. Pd-catalyzed asymmetric allylic substitutions of both acyclic and cyclic substrates were also examined using various nucleophiles such as malonate derivatives, nitromethane, aliphatic amines, and aromatic amines, providing a variety of chiral compounds with good to excellent enantioselectivity. In addition, Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were examined using structurally optimized P-chirogenic diaminophosphine oxides, and the corresponding branched products were obtained in a highly regio- and enantioselective manner. Furthermore, the developed catalytic asymmetric process was successfully applied to the catalytic enantioselective synthesis of biologically active compounds, (R)-preclamol, (R)-baclofen hydrochloride, and (-)-paroxetine.     

Gold‐Catalyzed Annulations of 2‐Alkynyl Benzaldehydes with Vinyl Ethers: Synthesis of Dihydronaphthalene,Isochromene, and Bicyclo[2.2.2]octane Derivatives

With the suitable selection of a gold catalyst as well as the appropriate control of the reaction conditions, various new gold‐catalyzed cyclizations of 2‐alkynyl benzaldehyde with acyclic or cyclic vinyl ethers have been developed. Acetal‐tethered dihydronaphthalene and isochromenes were obtained from the reactions of 2‐alkynyl benzaldehydes with acyclic vinyl ethers under mild conditions. And, more interestingly, the gold‐catalyzed reactions of 2‐alkynyl benzaldehyde with a cyclic vinyl ether afforded the bicyclo[2.2.2]octane derivative involving two molecules of cyclic vinyl ethers. These products contain interesting substructures that have been found in many biologically active molecules and natural products. In addition, a gold‐catalyzed homo‐dimerization of 2‐phenylethynyl benzaldehyde 1 a was observed when the reaction was carried out in the absence of vinyl ether, affording a set of separable diastereomeric products. Plausible mechanisms for these transformations are discussed; a gold‐containing benzopyrylium was regarded as the crucial intermediate by which a number of these new transformations took place.     

Study of luminescence properties of cyclic and acyclic thiadiazole-containing compounds

Luminescence properties of thiadiazole-containing compounds of cyclic and acyclic structure have been investigated. All compounds are characterized by fluorescence in the region 500–600 nm. The highest quantum yield of luminescence in the studied series is exhibited by acyclic product of the ABA type (where A is thiadiazole cycle, B is isoindole cycle) with N-pentylthiadiazoline fragments.     

Syntheses of Chiral Acyclic Natural Products from Sugar

The syntheses of several biologically interesting acyclic natural products such as LTA, 1, LTB₄ 8, mosquito oviposition attractant pheromone 46 and cytotoxic annonaceous acetogenin corossolone 57 and corossoline 58 from sugars in our laboratory are reviewed.     

产甘油基因工程菌的构建

利用途径工程的基本原理,在大肠杆菌中构建一条产甘油的新代谢途径。从酿酒酵母Sacchdromyces cerevisiae INVSc1菌株总DNA克隆3-磷酸甘油脱氢酶基因(gpdl)和3-磷酸甘油酯酶基因(hot2),构建由两个杂合启动子trc启动基因的双表达盒的重组质粒pGEM-Cgpd1-Chor2,后者转入E．coli JM109菌株,构建的重组菌株就具有一条直接将葡萄糖转化为甘油的新代谢途径,将该重组菌株以葡萄糖为底物进行摇瓶发酵,甘油产率为1．18g／L。该研究结果为进一步构建生产1,3-丙二醇工程菌打下了基础。     

One‐Step Synthesis of 2,5‐Diaminoimidazoles and Total Synthesis of Methylglyoxal‐Derived Imidazolium Crosslink (MODIC)

Here we describe a general method for the synthesis of 2,5‐diaminoimidazoles, which involves a thermal reaction between α‐aminoketones and substituted guanylhydrazines without the need for additives. As one of the few known ways to access the 2,5‐diaminoimidazole motif, our method greatly expands the number of reported diaminoimidazoles and further supports our previous observations that these compounds spontaneously adopt the non‐aromatic 4(H) tautomer. The reaction works successfully on both cyclic and acyclic amino ketone starting materials, as well as a range of substituted guanylhydrazines. Following optimization, the method was applied to the efficient synthesis of the advanced glycation end product (AGE) methylglyoxal‐derived imidazolium crosslink (MODIC). We expect that this method will enable rapid access to a variety of biologically important 2,5‐diaminoimidazole‐containing products.     

Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions

Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.     

A new method for the activation of ethyl benzenesulfenate in electrophilic addition reactions

Reactions of unsaturated compounds with the PhSOEt-SOHal₂ and PhSOEt-Me₃SiHal systems (Hal = Cl or Br) were proposed as a new route to haloalkyl phenyl sulfides. With acyclic and mono- and bicyclic alkenes and dienes as examples, the regio- and stereoselectivity of the reactions were studied.     

Novel Pyrrolo[2,3-d]pyrimidine Ring forming Methodology

A short, succinct route to biologically active and medicinally important pyrrolo[2,3-d]pyrimidines has been developed starting from readily available acyclic aldehydes. A very efficienttwo step sequence involving a Knoevenagel condensation followed by copper mediated 1,4-conjugate of vinyl magnesium bromide sets up the acyclic precursor. Then, guanidine cyclization followed by a palliduim catalyzed amination reaction or ozonolytic cleavage of the vinyl substituent followed by guanidine cyclization and intramolecular imine formation complete the synthesis.