Design and synthesis of novel α-substituted phosphonic acids catalyzed by nano zinc oxide

A series of α-substituted phosphonic acids were synthesized by a reaction between dimedone, aromatic aldehydes, and triethylphosphite in ethanolic solution under reflux conditions and using nano zinc oxide as a catalyst. Their structures were determined by Infrared, carbon, hydrogen, nitrogen, and sulfur analysis, ¹H-NMR, ¹³C-NMR, and ³¹P-NMR.     

Design,green synthesis,anti-microbial,and anti-oxidant activities of novel α-aminophosphonates via Kabachnik-Fields reaction

An efficient and environmentally friendly protocol has been developed for the synthesis of novel α-aminophosphonates in good to excellent yields (76–92%) by a one-pot, three-component reaction of an amine, an aldehyde, and diphenyl phosphite using polyethylene glycol (PEG-400) as a green solvent at 80°C via Kabachnik-Fields reaction. Their chemical structures were elucidated by IR, ¹H, ¹³C, and ³¹P NMR spectroscopy, mass spectrometry, and elemental analysis. The titled compounds displayed moderate to high anti-microbial and anti-oxidant activities.     

Design and synthesis of α-carboxy phosphononucleosides

Rhodium catalyzed O-H insertion reactions employing α-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an α-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.     

Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception

Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC50) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy ...     

Organocatalytic synthesis of α-quaternary amino acid derivatives via aza-Friedel-Crafts alkylation of indoles with simple α-amidoacrylates

The first (organo)catalytic method for regio- and chemoselective aza-Friedel-Crafts (FC) alkylation of indoles and pyrroles with commercially available methyl α-acetamidoacrylates has been discovered. It minimizes/eliminates common competing reactions that occur due to the high and multiatom-nucleophilic character of indole and pyrrole. Diverse quaternary α-amino acids were successfully prepared in good yield and high selectivity using low catalyst loading. The enantioselective variant using BINOL-derived phosphoric acids was also explored with indole providing the desired F-C alkylation product with moderate enantioselectivities.     

Expeditious and novel synthesis of α-hydroxyesters via rhodium–NHC catalyzed arylation of ethyl glyoxalate

The rhodium–NHC catalyzed arylation reaction of ethyl glyoxalate with aryl and alkyl boronic acids provides an efficient method for the synthesis of α-hydroxyesters. A wide range of α-hydroxyesters (up to 12) were prepared in good to excellent yields. KO^tBu was the base of choice, along with tert-amyl alcohol as the solvent. As far as we are aware, this is the first report of this catalytic arylation, using rhodium–NHC catalysts with this specific substrate type.     

Design, synthesis and antifungal activity of novel triazole derivatives

Twenty-three 1 -(1H-1,2,4-triazole-1 -y1)-2-(2,4-difluorophenyl)-3-(iV-cycloproyl-N-substituted-amino)-2-propanols were designed and synthesized on the basis of the active site of lanosterol 14α-demethylase. In vitro antifungal activities showed that some of the title compounds had higher antifungal activity and broader antifungal spectrum than fluconazole.     

Highly efficient synthesis of polysubstituted 1,2-dihydroquinolines via cascade reaction of α-ketoesters with arylamines mediated by iodine

An efficient strategy enabling the construction of polysubstituted 1,2-dihydroquinoline derivatives mediated by the commercially available, economical, and environmentally benign iodine (3 mol %) under mild conditions was developed. Various arylamines and α-ketoesters could participate in this cascade reaction, and the desired products were obtained in excellent yields up to 98%.     

A practical synthesis of novel α-dibromoalkyl- and trimethylsilylmethyl-aminoboranes and derivatives

Addition of LDA to a mixture of trimethylborate and dibromomethane in THF at a temperature of -78°C leads to the formation of dibromomethyllithium and its capture by borate ester. ClB(OMe)(2) converts the resulting borate salt to dimethoxy(dibromomethyl)borane 2. N,N-Dimethylamino(methoxy)(dibromomethyl)borane 3 and N,N-bis(dimethylamino)(dibromomethyl)borane 4 were prepared by an amination reaction between N,N-dimethylaminotrimethylsilane and dimethoxy(dibromomethyl)borane 2. To obtain dichlorotrimethylsilylmethylborane 7 not containing the α-halomethyl group, N,N-bis(dimethylamino)(trimethylsilylmethyl)borane 5 was first obtained from the reaction of ClB(NMe(2))(2) with an organolithium reagent. Dimethoxy(trimethylsilylmethyl)borane 6 was then prepared by methoxylation of compound 5. Finally, compound 7 was prepared by chlorination of 6 using BCl(3). The chemical structures of these compounds were determined using (13)C, (1)H, (11)B NMR and GC/MS/MS techniques.     

A general stereoselective enamine mediated alkylation of α-substituted aldehydes

We herein present a general enamine-mediated α-alkylation of α-substituted aldehydes with carbenium ions for the stereoselective construction of quaternary stereogenic centers.     

Selective synthesis of α-fluoro-β-keto- and α-fluoro-β-aminophosphonates via electrophilic fluorination by selectfluor

A series of α-mono- and α,α-difluoro-β-ketophosphonates were synthesized in moderate to good yields with excellent selectivities via electrophilic fluorination by Selectfluor. Subsequently, synthetic potential of the obtained α-monofluoro-β-ketophosphonates was demonstrated by their application in synthesis of α-monofluoro-β-aminophosphonates, useful building blocks in the preparation of phosphapeptides.     

Solid-phase synthesis of α-alkylserines via phase-transfer catalytic alkylation of polymer-supported 2-phenyl-2-oxazoline-4-carboxylate

Described is the development of a new solid-phase synthetic method for α-alkylserines in which phase-transfer catalytic alkylation of polymer-supported 2-phenyl-2-oxazoline-4-carboxylate (12) is the key step. The easy preparation of the polymer-supported substrate 12, the high chemical yield (up to 93%), and the mild cleavage conditions could make this method very practical for the synthesis of α-alkylserines.     

Catalytic asymmetric synthesis of cyclic α-alkyl-amino acid derivatives by C,N-double alkylation

Catalytic asymmetric synthesis of various cyclic α-alkyl-amino acid derivatives having a tetrasubstituted α-carbon, such as α-alkylprolines has been accomplished by asymmetric phase-transfer C-alkylation of α-alkyl-amino acid derivatives and subsequent intramolecular N-alkylation.     

Design,synthesis and cholinesterase inhibitory activity of α-mangostin derivatives

Abstract

α-mangostin, a polyphenol xanthone derivative, was mainly isolated from pericarps of the mangosteen fruit (Garcinia mangostana L.). In present investigation, a series of derivatives were designed, synthesised and evaluated in vitro for their inhibitory activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among the synthesised xanthones, compounds 1, 9, 13 and 16 showed AChE selective inhibitory activity, 15 was a BuChE selective inhibitor while 2, 3, 5, 6, 7, 12 and 14 were dual inhibitors. The most potent inhibitor of AChE was 16 while 5 was the most potent inhibitor of BuChE with IC₅₀ values of 5.26?μM and 7.55?μM respectively.     

A novel olefination of carbonyl compounds with α-bromoacetic ester mediated by tri-n-butylstibine

Tri-n-butylstibine has been found to mediate the olefinatlon of carbonyl compounds by α-bromoacetic ester to give corresponding olefins in good yields.     

Selective synthesis of α-methylenyl zirconacyclopentene via cross-coupling of alkyne and allene

α-Methylenyl zirconacyclopentenes are synthesized regio- and stereoselectively via reductive intermolecular cross-coupling of alkynes and allenes promoted by zirconocene species ‘Cp₂Zr’. An interesting reductive intramolecular coupling of the α-methylenyl zirconacyclopentene has been observed in the presence of DMAD/CuCl, resulting in the generation of cyclobutene with an exocyclic double bond. Polysubstituted 1,4-dienes can be given with high selectivity and good yields.     

Design, synthesis and molecular docking studies of novel triazole antifungal compounds

Based on the active site of Candida albicans lanosterol 14α-demethylase (CACYP51), novel triazole compounds structurally different from the current triazole drugs were designed and synthesized. In vitro antifungal activities showed that compounds 10,11, 16 and 20 exhibited strong activities. In addition, compounds 10,11 and 16 also displayed certain activities against fluconazole-resistant fungi.     

Design and synthesis of novel tweezer anion receptors based on deoxycholic acid

A novel type of molecular tweezer receptors based on deoxycholic acid has been designed and synthesized and their binding properties were examined by UV-vis spectral titration. These molecular tweezers showed a high selectivity toward F- over Cl-,Br-, I-, AcO-, H2PO4-.