Lossen Rearrangement Research Articles

Ethylenediamine-Derived Chromatographic Ligand to Separate BSA, Lysozyme, and RNase A

Chromatography has become an essential tool for the purification of proteins, since most purification schemes involve some forms of this methodology. Recently, using chromatographic matrices prepared from symmetrical aminosquarylium cyanine dyes immobilized on Sepharose via a central alkylamino residue, we were able to isolate lysozyme, α-chymotrypsin and trypsin from a mixture. Following this, we envisioned that the immobilization of an asymmetric squarylium dye bearing an N-carboxyethyl group in one of its ending nuclei, on ethylenediamine-activated Sepharose, through EDC/NHS amidation coupling, could enhance the ligand’s mobility and improve the interactions with the target proteins. The prepared support was found to separate an artificial mixture of BSA, lysozyme, and RNase A. Unexpectedly, the support prepared in the absence of the dye exhibited a separation performance similar to that of the dyed support, contrary to that observed in all previous studies using cyanine dyes as ligands for affinity chromatography, which prompted us to try to determine the structural molecular constitution of the matrix surface. A synthetic route to the final chromatographic support could be devised, which is believed to consist in the cyclization of two nearby ethylenediamine units, involving the inclusion of a succinimide-derived residue between them and the EDC-mediated Lossen rearrangement of an intermediary hydroxamic acid.

Olefin cross-metathesis as a valuable tool for the preparation of renewable polyesters and polyamides from unsaturated fatty acid esters and carbamates

Olefin cross-metathesis of unsaturated fatty acid methyl ester (FAME) derived benzyl carbamates with methyl acrylate is described. The obtained by-product, an α,β-unsaturated ester, was further modified via thia-Michael addition reactions in order to synthesize branched AA-type or AB-type monomers for the preparation of polyesters, which are tuneable by oxidation. Cross-metathesis of fatty acid derived carbamates was used as a novel approach to prepare linear AB-type monomers, which can be used for the preparation of renewable polyamides PA11, PA12 and PA15. The necessary fatty acid carbamates were prepared by applying a catalytic Lossen rearrangement procedure. The presented synthesis strategy has potential for the bio-sourced preparation of monomers for the production of polyamides. All prepared polymers were fully characterized by NMR, SEC, and DSC analyses. Additionally, the Young's modulus of the prepared long-chain polyamide PA15 was determined.

Ethyl 2-Cyano-2-(4-nitrophenylsulfonyloxyimino)acetate-Mediated Lossen Rearrangement: Single-Pot Racemization-Free Synthesis of Hydroxamic Acids and Ureas from Carboxylic Acids

Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY) mediated Lossen rearrangement and its application for the synthesis of ureas is demonstrated. Required hydroxamic acids for the Lossen rearrangements were synthesized from carboxylic acids using the same reagent. Finally, reaction of an amine with the produced isocyanate resulted in urea. Good yields without racemization were achieved under milder and simpler reaction conditions. Reactions are compatible with common N-protecting groups, such as Boc, Fmoc, Cbz, and benzyl, as well as various OH protecting groups, such as (t)Bu and Bzl. Conversion from carboxylic acid to urea is achieved in one pot. Most importantly, byproducts Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] and 4-nitrobenzenesulfonic acid can be recovered easily and can be recycled to prepare the reagent. Thus, the method is environmentally friendly and cost-effective.

An easy access to unsymmetrical ureas: a photocatalytic approach to the Lossen rearrangement

An efficient and operationally simple method for the synthesis of unsymmetrical ureas from various hydroxamic acids and amines has been developed. Plausibly, the protocol involves visible-light-initiated in situ formation of Vilsmeier–Haack reagent and COBr2 with CBr4 and a catalytic amount of DMF in the presence of Ru(bpy)3Cl2 as a photocatalyst to bring about the Lossen rearrangement at room temperature.

Renewable Non‐Isocyanate Based Thermoplastic Polyurethanes via Polycondensation of Dimethyl Carbamate Monomers with Diols

1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)-catalyzed polycondensation reactions of fatty acid derived dimethyl dicarbamates and diols are introduced as a versatile, non-isocyanate route to renewable polyurethanes. The key step for the synthesis of dimethyl carbamate monomers from plant-oil-derived dicarboxylic acids is based on a sustainable base-catalyzed Lossen rearrangement. The formed polyurethanes with molecular weights up to 25 kDa are characterized by SEC, DSC, and NMR analysis.

ChemInform Abstract: N‐Methylimidazole‐Catalyzed Synthesis of Carbamates from Hydroxamic Acids via the Lossen Rearrangement.

An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.

ChemInform Abstract: Introducing Catalytic Lossen Rearrangements: Sustainable Access to Carbamates and Amines.

AbstractA novel, highly efficient and environmentally benign procedure of the Lossen rearrangement is developed.

N-Methylimidazole-catalyzed Synthesis of Carbamates from Hydroxamic Acids via the Lossen Rearrangement

An efficient, one-pot, N-methylimidazole (NMI) accelerated synthesis of aromatic and aliphatic carbamates via the Lossen rearrangement is reported. NMI is a catalyst for the conversion of isocyanate intermediates to the carbamates. Moreover, the utility of arylsulfonyl chloride in combination with NMI minimizes the formation of often-observed hydroxamate-isocyanate dimers during the sequence. Under the present conditions, lowering of temperatures is also possible, enabling a mild protocol.

Introducing Catalytic Lossen Rearrangements: Sustainable Access to Carbamates and Amines

AbstractA new, highly efficient and environmentally benign catalytic variant of the Lossen rearrangement is described. Dimethyl carbonate (DMC) as green activation reagent of hydroxamic acids in presence of catalytic amounts of tertiary amine bases {1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), 1,8‐biazabicyclo 5.4.0 undec‐7‐ene (DBU), 1,4‐diazabicyclo[2.2.2]octane (DABCO), and triethylamine} and small quantities of methanol initiate the rearrangement. Methyl carbamates were obtained in good to moderate yields when aliphatic hydroxamic acids were employed in this catalytic Lossen rearrangement; under the same conditions aromatic hydroxamic acids yielded anilines. Notably, the mixture of DMC/methanol was recycled several times without observing decreased yields, thus minimizing the produced waste. Moreover, several other organic carbonates were successfully employed in the introduced catalytic Lossen rearrangement procedure.

Reaction Mechanisms between Halogenated Quinoid Carcinogens and Hydroxamic Acids: From Lossen Rearrangement to an Unexpected Radical Pathway

Reaction Mechanisms between Halogenated Quinoid Carcinogens and Hydroxamic Acids: From Lossen Rearrangement to an Unexpected Radical Pathway

ChemInform Abstract: Bromodimethylsulfonium Bromide (BDMS)‐Mediated Lossen Rearrangement: Synthesis of Unsymmetrical Ureas.

AbstractBDMS serves as a safe and efficient reagent for in situ generation of isocyanates via Lossen rearrangement of hydroxamic acids.

Substrate-dependent divergent outcomes from catalytic reactions of silyl-protected enol diazoacetates with nitrile oxides: azabicyclo[3.1.0]hexanes or 5-arylaminofuran-2(3H)-ones.

Dirhodium(II)-catalyzed reactions of silyl-protected enol diazoacetates with nitrile oxides exhibit high nitrile oxide substituent dependence in the production rearrangement products via dipolar cycloaddition and either the Neber rearrangement or the Lossen rearrangement.

ChemInform Abstract: Unexpected Catalytic Reactions of Silyl‐Protected Enol Diazoacetates with Nitrile Oxides that Form 5‐Arylaminofuran‐2(3H)‐one‐4‐carboxylates.

Silyl-protected enol diazoacetates undergo dirhodium(II)-catalyzed reactions with nitrile oxides to form acid-labile ketenimines via dipolar cycloaddition of nitrile oxides to a donor/acceptor cyclopropene and Lossen rearrangement of the dipolar adduct; acid catalysis converts the ketenimine to the furan product.

Bromodimethylsulfonium bromide (BDMS)-mediated Lossen rearrangement: synthesis of unsymmetrical ureas

Bromodimethylsulfonium bromide (BDMS) was found to be a very efficient reagent for Lossen rearrangement of hydroxamic acids to the corresponding isocyanates which were subsequently trapped in situ with various amines to afford unsymmetrical ureas in good to excellent yields (64–89%). The protocol is experimentally simple, mild, and represents valuable alternative to the existing methods for in situ activation of hydroxamic acids promoting Lossen rearrangement.

Metal-assisted Lossen Rearrangement

A new reaction mechanism for the Lossen rearrangement of hydroxamic acids catalyzed by basic salts is presented. It is shown that the rearrangement proceeds in metal complexes of deprotonated hydroxamic acids. The deprotonation can occur either at the oxygen atom (observed for the zinc complexes) or at the nitrogen atom (observed for the potassium complexes). Both anionic forms are characterized by infrared multiphoton dissociation spectroscopy. The rearrangements proceed from the reactive N-deprotonated metal hydroxamates and lead to metal carbamates. The mechanism is elucidated by computational chemistry, mass-spectrometric studies, and preparative experiments.

Unexpected catalytic reactions of silyl-protected enol diazoacetates with nitrile oxides that form 5-arylaminofuran-2(3H)-one-4-carboxylates.

Silyl-protected enol diazoacetates undergo dirhodium(II)-catalyzed reactions with nitrile oxides to form acid-labile ketenimines via dipolar cycloaddition of nitrile oxides to a donor/acceptor cyclopropene and Lossen rearrangement of the dipolar adduct; acid catalysis converts the ketenimine to the furan product.

An Efficient Synthesis of Biologically ActiveTetrachloroquinazolin-2,4-dione

Pyrimidine is a prominent member of the diazine family of heterocyclics. Pyrimidine compounds have been explored for use as histamine and adenosine receptor antagonists as well as among several other biological receptors and modulators. The aim of the current research work was to synthesize a new set of tetrachloroquinazolin-2,4-dione derivatives by treatment of N-phenylsulphonyloxytetrachlorophthalimide with some primary aliphatic and aromatic amines via Lossen Rearrangement. The structures of the synthesized compounds were characterized using physical and spectral data such as IR, 1H NMR and mass spectral studies. The newly synthesized compounds were evaluated for their preliminary in vitro antibacterial activity towards Salmonella typhi, Staphylococcus aureus and Bacillus cereus. This study leads us to conclude that quinazolinediones have interesting biological and pharmacological properties towards bacteria.

Synthesis and reactions of 3-aminotetrachloroquinazolin-2,4-dione

N -phenylsulphonyloxytetrachlorophthalimide was obtained by treatment of N -hydroxy tetrachlorophthalimide with benzenesulphonyl chloride. Also, the titled compound 3 was obtained by reaction of compound 2 with hydrazine hydrate via Lossen rearrangement. Compound 3 used as starting material for the synthesis of new pyrimidine and quinazolinedione derivatives containing four chlorine atoms which have pharmacological activity.

Abstract 3691: Selective depletion of mutant p53 by isothiocyanates and its structure-activity relationships

Abstract It has been shown that isothiocyanates (ITCs), derived from hydrolysis of glucosinolates in cruciferous vegetables via Lossen rearrangement by myrosinase, induce apoptosis in cancer cells. We here demonstrate that certain naturally-occurring ITCs selectively deplete mutant p53, but not the wild type, and do so via a post-transcriptional mechanism. Direct p53 binding and the sequential conformational changes appears to be one of the mechanisms by which mutant p53 is depleted. Structure-activity relationship studies (SARs) using naturally-occurring and synthetic ITCs show that depletion is influenced by the structure of the ITC side chain moiety. Consistent with the gain of function by mutant p53, we show that cells with p53 mutations are more sensitive to the cytotoxicity of phenethylisothiocyanate (PEITC) than are those with the wild type. Furthermore, 2,2-diphenylethyl ITC, a synthetic ITC and one of the most potent depletors of mutant p53 studied, induces apoptosis to the greatest extent in breast cancer cells with mutant p53 status. Collectively, this study shows that mutant p53 depletion may be an important novel target for cancer chemoprevention and therapy by natural and synthetic ITCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3691. doi:10.1158/1538-7445.AM2011-3691

ChemInform Abstract: 1‐Propanephosphonic Acid Cyclic Anhydride (T3P) as an Efficient Promoter for the Lossen Rearrangement: Application to the Synthesis of Urea and Carbamate Derivatives.

AbstractA convenient procedure is presented for the conversion of aromatic acids and amino acids into hydroxamates using T3P as activator.