A General Way,From L-Ascorbic And D-Isoascorbic Acids,To Homochiral α-Hydroxy, α,β-Dihydroxy And α,β-Epoxy-Aldehydes,Useful Building Blocks For The Synthesis Of Linear Oxygenated Fatty Acids Metabolites

Abstract

Enantiomerically pure α-hydroxy, α,β-dihydroxy and α,β-epoxyaldehydes, useful building blocks for the synthesis of acyclic oxygenated fatty acids metabolites, were synthetized via epoxybutanediol acetonide starting from the commercially available L-ascorbic and D-isoascorbic acids.     

Solid-phase peptide synthesis in water. Part 3: A water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl tetrafluoroborate, and its application to solid phase peptide synthesis in water

Chemical synthesis of peptides has been performed in various organic solvents, but the safe disposal of organic solvents is now an important environmental issue. Our aim is to be able to perform solid-phase peptide synthesis in water. For this, we have designed a new water-soluble N-protecting group, 2-[phenyl(methyl)sulfonio]ethoxycarbonyl (Pms), and have studied its introduction onto amino acids. Pms-amino acids were prepared by treating 2-(phenylthio)ethoxycarbonyl amino acids with methyl iodide in the presence of silver tetrafluoroborate. Because sulfur-containing amino acids, such as Met and Cys, were modified by the reaction, we designed a new reagent, 2-[phenyl(methyl)sulfonio]ethyl-4-nitrophenyl carbonate, to introduce the Pms group on amino acids. This reagent is a stable crystalline material and its introduction onto amino acids (including sulfur-containing amino acids) was successful. The solid-phase synthesis of Leu- and Met-enkephalin amides using Pms-protected amino acids was successfully achieved in water.     

N,N-Dimethylchlorosulfitemethaniminium chloride (SOCl2-DMF) a versatile dehydrating reagent.

N,N-dimethylchlorosulfitemethaniminium chloride formed from thionyl chloride and dimethylformamide was found and efficient reagent for the synthesis of acyl azides from carboxylic acids and nitriles from oximes. It is also highly efficient for the direct synthesis of beta-lactams from carboxylic acids and imines avoiding the use of acid chlorides.     

Thermally expanded graphite: Synthesis, properties, and prospects for use

Results obtained in synthesis of thermally expanded graphite by chemical and electrochemical methods with sulfuric and nitric acids are summarized. The possibility of controlling the properties of thermally expanded graphite compounds in electrochemical synthesis is demonstrated. The existing and promising application areas of thermally expanded graphite are analyzed.     

gem-Dibromomethylarenes: a convenient substitute for noncommercial aldehydes in the knoevenagel-doebner reaction for the synthesis of alpha,beta-unsaturated carboxylic acids

A facile synthesis of alpha,beta-unsaturated carboxylic acids from gem-dibromomethylarenes is described. gem-Dibromomethylarenes are employed for the first time in the Knoevenagel-Doebner reaction as aldehyde equivalents for the efficient synthesis of alpha,beta-unsaturated carboxylic acids.     

A novel three-component reaction of allenoates, isocyanides, and carboxylic acids: facile synthesis of highly substituted acryl imide derivatives

A novel synthesis of highly substituted acryl imide derivatives by the three-component reaction of allenoates, isocyanides, and carboxylic acids was reported, and the intramolecular cyclization reaction of allenoic acids with isocyanides was also described.     

The Computer-Aided Design,Synthesis, and Activity Prediction of New Leucine Aminopeptidase Inhibitors

The design, stereo-, and enantioselective synthesis and activity prediction of aminophosphonic acids as new leucine aminopeptidase inhibitors will be discussed.     

Synthesis and mass spectrometry of benzoxazoline, dimethyloxazoline and 4-phenyloxazoline derivatives of polyunsaturated fatty acids

Cyclic nitrogen moieties have proved to be of great value for the mass spectrometric location of double bonds in polyunsaturated fatty acids. However, their synthesis has traditionally required long reaction times and/or high temperatures. Recently, we introduced a one-pot, high-yield, mild and efficient method for the synthesis of various fatty acid amide derivatives. We have now extended this procedure to include the synthesis of benzoxazoline, dimethyloxazoline and 4-phenyloxazoline analogs of a series of fatty acids containing 18 to 22 carbon atoms and 0 to 6 double bonds. A comparison of the mass spectral properties of the three derivatives of these saturated and unsaturated fatty acids is described.     

Oxidation of Alkynyl Boronates to Carboxylic Acids,Esters, and Amides

A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)−B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.     

Oxidation of Alkynyl Boronates to Carboxylic Acids,Esters, and Amides

A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.     

Design, synthesis, and evaluation of a new generation of modular nucleophilic glycine equivalents for the efficient synthesis of sterically constrained alpha-amino acids

A new generation of modular achiral glycine equivalents have been evaluated with respect to their synthetic utility for the production of tailor-made, sterically constrained alpha-amino acids, which proved to be the most efficient approach developed to date for the synthesis of symmetrical alpha,alpha-disubstituted-alpha-amino acids. Among the new series of achiral glycine equivalents, one was found to be a superior glycine derivative for the Michael additions with various (R)- or (S)-N-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones representing a general and practical synthesis of sterically constrained beta-substituted pyroglutamic acids. In particular, the application of these complexes allowed for the preparation of several beta-substituted pyroglutamic acids which include electron-releasing and sterically demanding substituents in the structure thus increasing the synthetic efficiency and expanding the generality of these Michael addition reactions.     

A novel synthesis of N-methyl asparagine,arginine, histidine,and tryptophan

[reaction: see text] N-Methyl amino acid residues in peptides modify several pharmacologically useful parameters, but synthesis of alkylated peptides is hampered by unavailability of N-methylated monomers. The syntheses of four N-methyl amino acids with basic side chains are presented. The side chains of these basic amino acids needed to be specially protected or constructed. This completes the set of 20 common L-amino acid N-methyl derivatives prepared via 5-oxazolidinone intermediates by our group.     

Stereoselective synthesis of GABOB,carnitine and statine phosphonates analogues

γ-Amino acids such as GABA, GABOB, statine and carnitine have attracted considerable attention as biologically active compounds. Over the last few years, significant interest in the stereoselective synthesis of γ-aminophosphonic acids GABOB^P, phosphocarnitine, phosphostatine and derivatives has been observed. An overview of synthetic approaches of γ-aminophosphonic acids and derivatives is presented. Data on the practical applications of the γ-aminophosphonic acids are also discussed.     

Pursuit of optimal carbohydrate-based anticancer vaccines: preparation of a multiantigenic unimolecular glycopeptide containing the Tn, MBr1, and Lewis(y) antigens.

A novel preparation of nonnatural glycoamino acids starting from n-pentenyl glycosides is described. The approach involves a Horner-Emmons olefination with a suitably protected glycine-derived phosphonate, followed by catalytic asymmetric hydrogenation, which proceeds with excellent diastereomeric selectivity. The synthetic methodology was useful for the preparation of glycoamino acids containing the Tn antigen, the MBr1 antigen (Globo-H), the Le(y) antigen, and lactose. These glycoamino acids can also serve as units for peptide synthesis. The synthesis of polyvalent glycopeptides containing three different antitumor antigens is described (28 and 29), and these have been prepared for conjugation to carrier protein in order to access the immunogenicity for tumor immunotherapy applications.     

Oxidative intramolecular coupling of 2, 3-disubstituted phenyl acrylic acids and derivatives promoted by di-tert-butylperoxide

Polymethoxy-substituted phenanthrene-9-carboxylic acids or their methylate are key intermediates for the synthesis of tylophora alkaloids and their analogs. An intramolecular oxidative coupling reaction of unfunctionalized 2,3-disubstituted phenyl acrylic acids and derivatives promoted by di-tert-butylper- oxide gave above intermediates in high yields. The mild reaction conditions and easy purification procedures of this method provide a new approach for the synthesis of phenanthrenes.     

Synthesis and optical resolution of 2-aryl-2-fluoropropionic acids, fluorinated analogues of non-steroidal anti-inflammatory drugs (NSAIDs)

We report the synthesis of optically active 2-aryl-2-fluoropropionic acids 2 as non-epimerizable mimics of 2-arylpropionic acids 1, a class of compounds which have been widely used as non-steroidal anti-inflammatory drugs (NSAIDs). This is a continuation of our research involving the design, synthesis, and evaluation of chiral fluorine-containing organic molecules as effective analogues of pharmacologically important compounds.     

NEW SEMISYNTHETIC CEPHALOSPORINS WITH ANTIBACTERIAL,ANTIVIRAL AND ANTIFUNGAL ACTIVITY

Abstract

The synthesis of new derivatives of thiazolidine 2-alkylidene-4-on-5-acetamidocephalosporanic acids or thiazolidine 2-arylidenazino-4-on-5-acetamidocephalosporanic acids and their salts of general formula (I) has been achieved.     

Synthesis of Diels–Alder adducts of N-arylmaleimides by a multicomponent reaction between maleic anhydride, dienes, and anilines

Abstract  

We have carried out the synthesis and characterization of some hexahydroisoindolyl benzoic acids and their corresponding ethyl esters by a multicomponent reaction (MCR) between aminobenzoic acids or aminobenzoates, maleic anhydride, and isoprene in the absence of catalysts. According to additional experiments, the MCR takes place by sequential formation of N-arylmaleamic acids from the aminobenzoic acids or aminobenzoates and maleic anhydride, Diels–Alder adducts of the acids and isoprene, and finally the imides. The ¹H NMR data (coupling constants) of the adducts suggested that the preferred conformation of the corresponding cyclohexene rings is a syn-boat, a fact supported by a density functional theory (DFT) conformational analysis and DFT calculations of the spin–spin coupling constants of the corresponding conformers. Our MCR synthetic methodology was tested successfully in the synthesis of other adducts, for which cyclopentadiene and other anilines were employed.     

One pot direct synthesis of oxazolines, benzoxazoles, and oxadiazoles from carboxylic acids using the Deoxo-Fluor reagent

A one-pot, high yield direct synthesis of various 2-substituted oxazolines, benzoxazoles, and 2-oxadiazoles from carboxylic acids using Deoxo-Fluor reagent is described.     

Synthesis,chemistry, physicochemical properties and industrial applications of amino acid surfactants: A review

Surfactant use throughout mankind is extensive, from their initial applications as detergents extending to use in medicine, lubricant, cosmetics and even enhanced oil recovery. However, the image of surfactant use has in the past been tarnished by issues with low biodegradability and their synthesis from nonsustainable resources. Amino acid–based surfactants are a class of surfactants derived from a hydrophobe source coupled with simple amino acids, mixed amino acids from synthesis or from protein hydrolysates, and as such can be derived solely from renewable resources. There are several pathways for their synthesis and this allows for extensive structural diversity in this class of surfactants, resulting in widespread tuneable functionality in their physiochemical properties. This review includes the details of most of the available routes of synthesis for amino acid surfactants (AASs) and the impact of the diverse routes on their final physiochemical properties, including solubility, dispersability, toxicity and biodegradability. The diversity offered by the structural variation in AASs offers many exciting commercial opportunities for this ever-growing class of surfactants. It also includes a discussion on current and future potential uses of AASs.