Selective Bromination of Dehydroacetic Acid with N-Bromosuccinimide

Bromination of dehydroacetic acid has been carried out with N-bromosuccinimide under various conditions. The reactions led to selective bromination, thereby offering efficient synthesis of 3β-bromodehydroacetic acid (3), 3β,5-dibromodehydroacetic acid (4), 3β,3β-dibromodehydroacetic acid (5), and 3β,3β,5-tribromodehydroacetic acid (6).     

Stereoselective Synthesis of (1Z,3E)-2-Ethoxycarbonyl-Substituted 1,3-Dienes via Stille Coupling of (E)-α-Stannyl-α,β-Unsaturated Esters with Alkenyl Halides

Palladium-catalyzed hydrostannylation of alkynyl esters in benzene at room temperature gives stereoselectively (E)-α-stannyl-α,β-unsaturated esters 1 in good yields. (E)-α-Stannyl-α,β-unsaturated esters 1 are difunctional group reagents that undergo Stille coupling reactions with alkenyl halides 2 in the presence of Pd(PPh₃)₄ and CuI co-catalyst to afford stereoselectively (1Z,3E)-2-ethoxycarbonyl-substituted 1,3-dienes 3 in good yields.     

The Reaction of Electron-Deficient Cyclopropane Derivatives with Aromatic Amines

Abstract

N-Aryl-trans,trans-α-carboxyl-β-benzoyl-γ-aryl-γ-butyrolactams were synthesized in high yields with high stereoselectivity by the reaction of electron-deficient cyclopropane derivatives, cis-1-benzoyl-2-aryl-6,6-dimethyl-5,7-dioxo-spiro-[2 (a) Zhang , J. ; Blazecka , P. G. ; Davidson , J. G. First direct reductive amination of mucochloric acid: A simple and efficient method for preparing highly functionalized α,β-unsaturated γ-butyrolactams . Org. Lett. 2003 , 5 , 553 – 556 ; (b) Sarma, K. D.; Zhang, J.; Curran, T. T. Novel synthons from mucochloric acid: The first use of α,β-dichloro-γ-butenolides and γ-butyrolactams for direct vinylogous aldol addition. J. Org. Chem. 2007, 72, 3311–3318 . [Google Scholar] 5 (a) Chen , Y. L. ; Ding , W. Y. A simple approach to highly stereoselective synthesis of β γ-trans-γ-butyrolactones . Chem. J. Chin. Univ. 1998 , 19 , 1614 – 1616 ; (b) Chen, Y. L.; Ding, W. Y.; Cao, W. G.; Lu, C. Stereoselective synthesis of N-aryl-trans,trans-α-carboxyl-β-methoxycarbonyl-γ-aryl-γ-butyrolactones. Synth. Commun. 2002, 32, 1953–1960.  [Google Scholar]]-4,8-octadiones, with aromatic amines. The reaction mechanism was proposed.     

N-Aryl Modification in γ-Lactam: Design and Synthesis of Novel Monocyclic γ-Lactam Derivatives as Inhibitor for Bacterial Propagation

In search of novel γ-lactam antibacterial agents as non-β-lactam mimics of some γ-lactam antibiotics, N-aryl modification in the γ-lactam ring has been made to synthesize compounds 4–8 in two to six steps. Compound 4 was synthesized using the intermolecular Michael addition of diethyl N-(6-coumarinyl)-2-aminomalonate and 3-aryl/(2-heteroaryl)acryloyl chloride followed by intramolecular amidification. Hydrolysis and stereoselective decarboxylation of 4 resulted in the formation of trans- γ-lactam carboxylic acids (5), which on side chain homologation followed by saponification of the intermediate γ-lactam monoester (7) afforded γ-lactam carboxylic derivatives 8. Moderate to good bacterial growth inhibition was observed for some of the synthesized compounds against E. coli and S. aureus.     

SmI3-Catalyzed Addition of Amines to α,β-Unsaturated N-Acylbenzotriazoles

The addition of amines to α,β-unsaturated N-acylbenzotriazoles could be catalyzed by samarium triiodide (SmI₃) at ambient temperature. α,β-Unsaturated aliphatic N-acylbenzotriazoles afforded bis-addition products (β-amino amides), whereas N-cinnamoylbenzotriazoles gave acylated products (cinnamoylamides) exclusively.     

Facile synthesis of novel α-methylene-pyrazole-carboxylate substituted imines and trans-β-lactams: Versatile synthons for diverse heterocyclic molecules

A simple, facile, and high yielding stereoselective approach for the integration of α-methylene-pyrazole-carboxylates at the β-lactam nucleus is described. These monocyclic β-lactams have been synthesized by treatment of 2-phenoxy/benzylthio/phenylthio ethanoic acids or acetoxyacetyl chloride/phthalimidoacetyl chloride 5a–e with novel α-methylene-pyrazole-carboxylate imines 4a–c using Et₃N and POCl₃ in refluxing toluene. All of the newly synthesized α-methylene-pyrazole carboxylate imines 4a–c and their β-lactam derivatives 6a–h have been fully characterized by spectroscopic techniques such as FTIR, NMR (¹H, ¹³C, and ¹³C DEPT-135), 2D-NMR (COSY and HSQC), and elemental analyses (CHN). The cycloaddition reaction was found to be highly stereoselective leading to the exclusive formation of trans-β-lactams 6a–h and trans configuration was assigned with respect to coupling constant values of C3-H and C4-H. The novel β-lactams 6a–h bearing α-methylene-pyrazole-carboxylate ring system will serve as useful synthons for highly functionalized acids, acetohydrazides/pyrazolones, alcohols, pyrazole carboxamides, peptides, and promising biologically active agents.     

Facile strategy for the preparation of pyrazoline derivatives through phosphine-promoted [2 + 3] cycloaddition of dialkyl azodicarboxylates with β,γ-unsaturated α-keto esters

A facile phosphine-promoted [2?+?3] cycloaddition of dialkyl azodicarboxylates with β,γ-unsaturated α-keto esters was developed, and a series of pyrazoline derivatives were obtained with good yields under mild conditions. Furthermore, the scope of the cyclizations was investigated.     

Efficient synthetic route toward biologically active γ-carboline derivatives

An efficient and short route was established for the synthesis of anti-bovine viral diarrhea virus agents, namely 4-methyl-γ-carboline (SK4M) 1, 3-methyl-γ-carboline (SK3M) 2, 5-methyl-γ-carboline (SK5M) 3, and a new γ-carboline derivative 4, using thermal electrocyclization reaction as a key step. The evaluation of cytotoxicity of compound 4 against human cervical cancer cell line HeLa and leukemic cell line HL-60 furnished CC₅₀ value of 19.5 and 18.8 µM respectively.     

Stereoselective synthesis of novel monocyclic trans-3-halogenated-4-pyrazolyl-β-lactams: Potential synthons and promising biologically active agents

Stereoselective synthesis of novel monocyclic trans-3-halogenated-4-pyrazolyl-β-lactams 5 is described. The reaction of ketene derived from α-bromo/chloroethanoic acids 4 using POCl₃ and Et₃N with pyrazolyl substituted imines 3a–d in refluxing toluene resulted exclusive formation of trans-β-lactams through [2?+?2] through cycloaddition reaction. The chemical structures of all the newly synthesized β-lactams were verified on the basis of spectroscopic techniques such as FTIR, ¹H NMR, ¹³C NMR, and elemental analysis (CHN). The trans configuration of β-lactams 5 was assigned with respect to position of C3-H and C4-H. The novel β-lactams 5 are potential synthons for azetidines, aziridines, 3-unsubstituted azetidinones, 3-alkyl-halo-azetidinones, and promising biologically active agents.     

One-Pot Approach to the Conversion of Alcohols into α-Iodo-α,β-unsaturated Esters

(Carboethoxymethylene)triphenylphosphorane 1 can undergo the tandem reaction of iodination–oxidation–Wittig reaction with alcohol in the presence of N-iodosuccinimide (NIS) and manganese dioxide. The reaction constitutes a stereoselective one-pot procedure for the preparation of Z-configured α-iodo-α,β-unsaturated esters in good to excellent yield.     

Modified Pyridine-Substituted Coumarins: A New Class of Antimicrobial and Antitubercular Agents

Some new biologically potent coumarin derivatives 7a–f, 8a–f, and 9a–f bearing modified pyridine moieties (indeno[1,2-b]pyridine, 4-azaphenanthrene and benzofuro [3,2-b]pyridine) at the sixth position were designed and synthesized. All the synthesized compounds were assayed for their antimicrobial efficiency against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella typhi, Candida albicans, and Aspergillus niger. Most of the compounds showed appreciable antimicrobial activity against the tested strains. Compounds 8b, 8c, 9b, 9d, and 9f emerged as most proficient members of the series. The antitubercular activity for all the synthesized compounds was performed against Mycobacterium tuberculosis H37R_v. Compounds 8f, 9b, and 9f exhibited promising antitubercular activity. Consequently, synthesized derivatives were found to be worthy of further investigation.     

Synthesis of new α-hydroxyphosphonates and α-acetoxyphosphonates

A series of new α-hydroxyphosphonate (5–14) have been synthesized in high yields by reaction of β-chloro-α,β-unsaturated aldehydes (1–4) and trialkyl phosphite in the presence of chlorotrimethylsilane at room temperature under solvent-free conditions. In addition, compounds (5–14) were reacted with acetic anhydride in DBU to give the new α-acetoxyphosphonate derivatives (15–23). All these phosphonates (5–23) were obtained as mixtures of two (E and Z) isomers and fully characterized by multinuclear (¹H, ¹³C, and ³¹P) NMR, IR spectroscopy and HRMS.     

One-Pot,Fluoride-Promoted Wittig Reaction

A one-pot, fluoride-promoted Wittig reaction was developed. The reactions of ethyl α-bromoacetate with aliphatic, aromatic, and heteroaromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced α,β-unsaturated esters in good to excellent yields and E-stereoselectivity. Under the same conditions, reactions of ethyl α-bromopropionate, α-bromo acetonitrile, and α-bromoacetophenone with aliphatic and aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced the expected α,β-unsaturated derivatives in good E-stereoselectivity. The protocol was extended to semistabilized ylides and applied to the synthesis of some combretastatin analogs.     

Synthesis of Drim-7,9(11)-diene and Its Hydroxylated Derivatives

This article describes a new efficient synthesis of drim-7,9(11)-diene and its hydroxylated derivates from drim-8-en-7-one. Reduction of this ketone with NaBO₄ in the presence of CeCl₃ · 7H₂O afforded regio- and stereoselectively drim-8-en-7β-ol in a high yield. Its dehydration with H₂SO₄ under mild conditions led to drim-7,9(11)-diene. Noncatalytic oxidation of drim-7,9(11)-diene with OsO₄ and the catalytic oxidation with the pair OsO₄–NMO gave, in a high yield, depending on conditions, driman-7β,8β,9α,11-tetraol or its mixture with drim-7-en-9α,11-diol and drim-9(11)-en-7α,8α-diol. Under optimal conditions the total yield of these diols reached 89%. The separate, noncatalytic oxidation of drim-7-en-9α,11-diol and of drim-9(11)-en-7α,8α-diol with OsO₄ afforded driman-7α,8α,9α,11-tetraol.     

Simultaneous Chiral Separation of Geometry Isomers and Enantiomers of Nateglinide by Capillary Electrophoresis with Mixture of CD Derivations as Chiral Selector

Abstract

A capillary electrophoresis (CE) method for the simultaneous separation of geometry isomers and enantiomers of nateglinide was built. Several different dyclodextrin (CD) derivatives were tested for the chiral separation of nateglinide, and it was proved that ionic CDs [i.e., carboxymethy-β-CD (CM-β-CD) and sulphonic-β-CD (S-β-CD)] could show better chiral selectivity for both geometry isomers and enantiomers than the neutral CDs. The separation of geometry of both isomers and enantiomers of nateglinide was obtained by CE in a 75-µm i.d. × 60 cm (effective length 45 cm) fused-silica capillary at 11 kV voltage, while 30 mM phosphate (pH = 8.38) acted as running buffer and a mixture of 40 mM S-β-CD + 21 mM CM-β-CD served as chiral selector. The detective wavelength was set at 254 nm.     

Determination of α-tocopherol in Cosmetic Products by Chronopotentiometry

Abstract

In the present study, a rapid chronopotentiometric method was developed for the determination of α-tocopherol in various cosmetic products. Determination of α-tocopherol is based on its irreverse oxidation by constant current at the planar glassy carbon electrode. The influence of the most important experimental parameters of chronopotentiometry was investigated. After optimization, an appropriate procedure for the sample preparation was developed. Under the defined experimental conditions, a detection limit of 7.5 mg L^?1 of α-tocopherol was obtained. The accuracy of the defined method was confirmed by means of recovery assay. The developed method was successfully applied to quantitation of α-tocopherol in various cosmetic products.     

Efficient Syntheses of a Series of Glycosphingolipids with 1,2‐trans‐Glycosidic Linkages

A series of glycosphingolipids with 1,2‐trans‐glycosidic linkages were synthesized in the presence of neighboring group participation using trichloroacetimidates as glycosyl donors and an azido‐sphingosine as the glycosyl acceptor. During the preparation of the target compounds, it was found that the α‐L‐arabinopyranosyl unit in target 7e and intermediates 7b–7d existed in the ¹ C ₄ conformation and that the β‐L‐fucopyranosyl unit in 10e adopted the ⁴ C ₁ conformation.     

K7[PW11CoO40]: Efficient and Ecofriendly Catalyst for the Enamination of β-Dicarbonyl Compounds

Condensation of a variety of β-dicarbonyl compounds with primary and secondary amines carried out in the presence of catalytic amounts of K₇[PW₁₁CoO₄₀]. From this reaction N-substituted β-enamino esters and ketones were obtained in high yields.     

Interactions of γ-Cyclodextrin with the Mixed Micelles of Anionic Surfactants and Their Inclusion Complexes Formation

Interactions of γ-cyclodextrin (γ-CD) with the single and mixed micelles of sodium dodecyl sulfate (SDS) and sodium lauroyl sarcosine (SLAS) have been studied at different concentrations of γ-CD by using conductivity measurements. From conductivity data, the pure and mixed critical micellar concentration (cmc), the equivalent ionic conductivities of the monomeric species (Λ _m), the associated species (Λ _assc) and the micelle (Λ _mic), the degree of counterion dissociation (χ) in the presence of γ-CD have been evaluated from the slope of the conductivity versus concentration plots for the pure and binary mixture of surfactants. From the dependence of cmc of the surfactantson γ-CD concentration, we have deduced the association constant (K) of surfactant-γ-CD inclusion complexes assuming 2:1 stoichiometry. Theories of Clint, regular solution, and Motomura's have been used for the evaluation of ideality or nonideality of the mixed system. Mixed micelles were found to be rich in SDS content in the presence and the absence of γ-CD. The cmc values have been used to evaluate the transfer of standard free energy of micelles (ΔG⁰ _M,tr) from the aqueous medium to additive medium.     

Solvent-free,one-pot synthesis of α,β-unsaturated esters in the presence of a C3-symmetric arsine

An efficient synthesis of α, β-unsaturated esters is achieved via a one-pot reaction in the presence of a C₃-symmetric arsine. The key advantages are the short reaction time, simple workup, mild reaction conditions, and high yields.