Home  About us  Contact
 

Intramolecular Attack (intramolecular + attack)

Distribution by Scientific Domains
Chemistry100%

Selected Abstracts

Synthesis of 2,4-difuryl-4H -3,1-benzothiazines via a furan ring migration reaction

JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2008
Vladimir T. Abaev
A new simple synthetic approach to 2,4-difuryl-4H -3,1-benzothiazines from 2-isothiocyanoaryldifuryl-methanes in the presence of acidic catalyst is described. This rearrangement is a new example of furan ring migration reaction resulting from intramolecular attack with electrophilic carbon. [source]

The role of the cyclic imide in alternate degradation pathways for asparagine-containing peptides and proteins

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007
Michael P. DeHart
Abstract Peptides and proteins exhibit enhanced reactivity at asparagine residues due to the formation of a reactive succinimide intermediate that produces normal and isoaspartyl deamidation products along with significant racemization. This study examines the potential for attack of amine nucleophiles at the succinimide carbonyls to generate alternate decomposition products, depending on the nucleophile involved in the reaction. The reactions of the model peptides Phe-Asn-Gly (FNG) and Phe-isoAsn-Gly (FisoNG) were explored as a function of pH (8.5,10.5) in the presence and absence of ammonia buffer (0.2,2 M) using an isocratic HPLC method to monitor reactant disappearance and product formation. In addition to deamidation to form isoAsp and Asp peptides, two additional types of reactions were found to occur via the succinimide intermediate under these conditions. Back-reaction of the succinimide with ammonia led to peptide backbone isomerization while intramolecular attack by the amino terminus produced diketopiperazines. A kinetic model assuming a central role for the succinimide intermediate was derived to fit the concentration versus time data. These studies implicate the cyclic imide as a key intermediate in the formation of alternate peptide and protein degradants, including possible covalent amide-linked aggregates that may form from intermolecular attack of the cyclic imide by neighboring amino groups. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2667,2685, 2007 [source]

Metal-Free and PdII -Promoted [2+3] Cycloadditions of a Cyclic Nitrone to Phthalonitriles: Syntheses of Oxadiazolines as well as Phthalamide,PdII and Dihydropyrrolyl-iminoisoindolinone,PdII Complexes with High Catalytic Activity in Suzuki,Miyaura Cross-Coupling Reactions

CHEMISTRY - A EUROPEAN JOURNAL, Issue 30 2008
Jamal Lasri Dr.
Abstract The previously unknown reactions between phthalonitriles, 1,2-(CN)2(C6)R1R2R3R41 (1,a, R1=R2=R3=R4=H; 1,b, R1=R2=R4=H, R3=CH3; 1,c, R1=R4=H, R2=R3=Cl; 1,d, R1=R2=R3=R4=Cl; 1,e, R1=R2=R3=R4=F), and a cyclic nitrone, ,O+NCHCH2CH2CMe22, proceed under heating in a sealed tube to give phthalimides 3, 2-oxadiazolyl-benzonitriles 4 or ortho -bis(oxadiazolyl)tetrafluorobenzene 4,e,. In the presence of palladium(II) chloride, phthalonitriles 1 react with 2 at room temperature, to give bis(pyrrolidin-2-ylidene)phthalamide PdII complexes 5 via metal-promoted rupture of the NO bond of the oxadiazoline ring. The ketoimine ligands thus generated can be liberated from the metal by displacement with a diphosphine. Although the first [2+3] cycloaddition of 2 to 1 can occur in the absence of the metal to give the mono-cycloadducts 4, the second [2+3] coupling at the still-unreacted cyano group requires its activation by coordination to PdII, affording complexes 6 containing two ligated oxadiazolyl-benzonitriles. These ligands undergo either i) further cycloaddition with 2 to afford ultimately (upon rearrangement) the bis(pyrrolidinylidene)phthalamide complexes 5 or ii) NO bond cleavage in the oxadiazoline ring with intramolecular attack of the imine nitrogen on the cyano carbon and bridging to a second PdII center to afford dimeric palladium(II) complexes 7, with chloride bridges, that bear a dihydropyrrolyl-iminoisoindolinone, a new type of ligand. The compounds were characterized by IR, 1H, and 13C,NMR spectroscopy, ESI MS or FAB+ MS, elemental analyses and, in the case of 4,c, 5,a, 5,c, and 7,c, also by X-ray diffraction analysis. Complexes 5,a and 7,c show high catalytic activity for the Suzuki,Miyaura cross-coupling reaction of bromobenzene and phenylboronic acid and give biphenyl in high yields with turnover frequencies (TOFs) of up to 9.0×105,h,1. [source]

Hydrolytic Reactions of Thymidine 5,- O -Phenyl- N -Alkylphosphoramidates, Models of Nucleoside 5,-Monophosphate Prodrugs

CHEMISTRY - A EUROPEAN JOURNAL, Issue 30 2007
Mikko Ora Dr.
Abstract To obtain detailed data on the kinetics of hydrolytic reactions of triester-like nucleoside 5,- O -aryl- N -alkylphosphoramidates, potential prodrugs of antiviral nucleoside monophosphates, the hydrolysis of diastereomeric (RP/SP) thymidine 5,-{O -phenyl- N -[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate} (3), a phosphoramidate derived from the methyl ester of L -alanine, has been followed by reversed-phase HPLC over the range from H0=0 to pH,8 at 90,°C. According to the time-dependent product distributions, the hydrolysis of 3 proceeds at pH<4 by two parallel routes, namely by nucleophilic displacement of the alaninyl ester moiety by a water molecule and by hydrolysis of the carboxylic ester linkage that allows intramolecular attack of the carboxy group on the phosphorus atom, thereby resulting in the departure of either thymidine or phenol without marked accumulation of any intermediates. Both routes represent about half of the overall disappearance of 3. The departure of phenol eventually leads to the formation of thymidine 5,-phosphate. At pH>5, the predominant reaction is hydrolysis of the carboxylic ester linkage followed by intramolecular displacement of a phenoxide ion by the carboxylate ion and hydrolysis of the resulting cyclic mixed anhydride into an acyclic diester-like thymidine 5,-phosphoramidate. The latter product accumulated quantitatively without any indication of further decomposition. Hydroxide-ion-catalyzed POPh bond cleavage of the starting material 3 occurred as a side reaction. Comparative measurements with thymidine 5,-{N -[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate} (4) revealed that, under acidic conditions, this diester-like compound is hydrolyzed by PN bond cleavage three orders of magnitude more rapidly than the triester-like 3. At pH>5, the stability order is reversed, with 3 being hydrolyzed six times as rapidly as 4. Mechanisms of the partial reactions are discussed. [source]