Facile ring-opening of N-acylisatins for the development of novel peptidomimetics

A range of novel mono- and bis-glyoxylamide peptidomimetics were prepared via the facile ring-opening of N-acylisatins with amino acids and peptide derivatives. The ring-opening of N-acylisatins with dipeptides and tripeptides was discovered to be the most efficient strategy for the synthesis of second and third generation glyoxylamides.     

Synthesis of optically active polynucleotide analogs with polytrimethylenimine backbones and thymine moieties

Polynucleotide analogs with polytrimethylenimine backbones and optically active 2-(thymin-1-yl)propionic acids as pendants were prepared. Linear polytrimethylenimines were obtained by ring-opening polymerization of 2-phenyl-5,6-dyhydro-4H-1,3-oxazine and subsequent hydrolysis of the resulting polymers. 2-(Thymin-1-yl)propionic acids were reacted with N-hydroxy succinimide to form active esters. Optical purities of active esters were determined by NMR with chiral chemical shift reagents. The polynucloetide analogs and related monomer and dimer model compounds were prepared by grafting reactions using active esters.     

Reactions of methylenecyclopropanes and vinylidenecyclopropanes with N-fluorodibenzenesulfonimide

Methylenecyclopropanes and vinylidenecyclopropanes undergo ring-opening reactions with N-fluorodibenzenesulfonimide (NFSI) upon heating at 60 °C in tetrahydrofuran to give the corresponding fluorinated derivatives 2 and 6 in good to excellent yields. A plausible reaction mechanism has been discussed on the basis of previous literature.     

Facile synthesis of 4-arylidene-5-imidazolinones as synthetic analogs of fluorescent protein chromophore

A facile and effective synthesis for a wide variety of 4-arylidene-5-imidazolinone derivatives was developed. 4-Arylidene-5-oxazolinones were prepared by Erlenmeyer azlactone synthesis from N-acylglycines and arylaldehydes. The ring-opening reactions of the 4-arylidene-5-oxazolinones with primary amines afforded 2-acylamino-3-arylacrylamides in excellent yields. A new dehydrative cyclization of the 2-acylamino-3-arylacrylamides in pyridine under reflux furnished the corresponding 4-arylidene-5-imidazolinones in good yields.     

Studies on the diastereoselective reductive alkylation of (R)-phenylglycinol derived phthalimide: observation of stereoelectronic effects

Full details of a flexible approach to N-protected (R)-3-alkyl-isoindolin-1-ones 13 via diastereoselective reductive-alkylation are described, with emphasis on the stereochemical outcome of the key diastereoselective reactions. Additional experiments allowed finding remarkable stereoelectronic effects on the reductive ring-opening reactions.     

Diferrocenylcyclopropenyl cations. Synthesis, structures, and some chemical properties

Synthesis of diferrocenylcyclopropenyl tetrafluoroborates with hetero-substituents in the three-membered ring, viz., ethoxy, trityloxy, ferrocenyl(phenyl)methoxy, N,N-diethylamino, piperidino, and morpholino, is described. The spatial structure of diferrocenyl(morpholino)cyclopropenyl tetrafluoroborate was established based on the data from X-ray diffraction analysis. Under the action of potassium tert-butoxide, all the diferrocenylcyclopropenyl tetrafluoroborates undergo three-membered ring-opening with formation of the corresponding 2,3-diferrocenylacrylic acid derivatives. A mechanism of the ring-opening is suggested.     

Nouveaux modeles polysilicies a partir d'indoles,du benzothiophene et du benzofuranne

Direct polysilylation of bicyclic heterosubstrates was performed without (in the case of indole or its N-methyl or N-trimethylsilyl derivatives) or with (benzothiophene, benzofuranne) ring-opening. Hexasilylation from benzothiophene occurred with desulfurization.     

Synthesis of α- -fucopyranosyl disaccharides with thioglycosidic linkages and characterization of α- -fucosidases from bovine kidney and epididymis by their inhibitory activities

Sulfur-linked disaccharide analogs of three α- -fucopyranosyl 2-acetamido-2-deoxy-β- -glucopyranosides and one α- -fucopyranosyl β- -galactopyranoside were synthesized by substitution reactions of sulfonates and ring-opening reactions of aziridine as well as oxirane derivatives using 1-thio-α- -fucopyranose as nucleophile. Fucosidases from bovine kidney and epididymis were inhibited by all of these disaccharide analogs and their Ki values range from 0.65 to 4.9 mM.     

Pyrazolinyl and cyclopropyl derivatives of protoporphyrin IX and chlorins related to chlorophyll a

Diazomethane reacts regioselectively with peripheral vinyl substituents of pyropheophorbide a and purpurin-18 N-methylimide to produce corresponding 1′-pyrazolinyl-substituted derivatives as a main product. Similarly, treatment of protoporphyrin IX gave a mixture of mono- and di-substituted pyrazolinyl analogs, which were isolated as individual products. Thermolytic decomposition of the pyrazolinyl derivatives produced cyclopropyl-substituted chlorins and porphyrins. 1,3-Dipolar cycloaddition mechanisms of the formation of 1′-pyrazolinyl derivatives are discussed.     

Stereoselective epoxidation of alkenylidene acetals derived from carbohydrates with d-allo,d-altro,d-galacto,d-gluco and d-xylo configurations

The synthesis of 2,3-epoxypropylidene acetals of sugar derivatives from N-acetyl-2-amino-2-deoxy-d-allopyranose, d-altropyranose, d-galactopyranose, N-acetyl-d-glucosamine, d-glucofuranose and d-xylofuranose is described. The epoxidation with m-CPBA of the corresponding alkenylidene derivatives took place with different stereoselectivities depending upon the sugar configuration, the protecting group of the hydroxyl groups of the sugar, and the substitution of the unsaturated system. The analysis of the ring-opening reaction of these oxiranes by hydrogenolysis enabled the assignation of their configuration at the new stereogenic centres.     

Synthesis of a 2-deoxy-ribose type 1-N-iminosugar

A 2-deoxy-ribose-type 1-N-iminosugar 5 was synthesized, in multi-gram scale, from fumaric acid monoethyl ester employing Sharpless asymmetric epoxidation followed by a Lewis acid-catalyzed (Yamammoto's aluminum reagent) cyanide epoxy ring-opening reactions.     

Synthesis of new <Emphasis Type="Italic">N</Emphasis>-glycosides based on Valproic acid analogs tetrazole derivatives

New N-glycosides based on valproic acid analogs tetrazole derivatives were synthesized. The bis-tetrazole derived from 1,6-hexandiol was also connected to acetylated glucose and formed bis-N-glycoside. Structures characterizations have been performed using FT IR, ¹H and ¹³C NMR spectroscopy.     

Atom-efficient synthesis of 2,6-diazacyclophane compounds through alcoholysis/reduction of 3-nitroarylmethylene-2,5-piperazinediones

Readily available cyclic dehydrodipeptides are convenient starting materials for atom-efficient synthesis of different compounds. A one-pot ring-opening/alcoholysis/hydrolysis process with 3-nitroarylmethylene-2,5-piperazinediones yielded N-3-nitroarylpyruvoylamino esters, which gave the corresponding amines by reduction of the nitro group. In the case of 2-nitroaryl compounds, an intramolecular reductive amination afforded N-indole-2-carbonylamino esters, while the intermolecular reductive amination of 3- and 4-nitroaryl derivatives allowed the synthesis of 2,6-diazacyclophanes. The amino compounds may be coupled with amino acids to get peptide-like derivatives.     

Synthesis of highly substituted pyrrolidines via palladium catalysed formal [2+3] cycloaddition of 5-vinyloxazolidin-2-ones to activated alkenes

Glycine-derived N-tosyl-5,5-divinyloxazolidin-2-one 10 undergoes a palladium catalysed decarboxylative ring-opening cyclization with strongly electron deficient alkylidenemalonate derivatives to give highly substituted pyrrolidines 14 containing two contiguous quaternary centres.     

Synthesis of β-lactams with π electron-withdrawing substituents

β-Lactams are crucial structural feature of β-lactam antibiotics and important intermediates in synthetic and pharmaceutical chemistry. Synthetic methods for β-lactams with π electron-withdrawing substituents, such as formyl (carbaldehyde), acyl, imino, carboxylic acids, carboxylates, carboxamides, cyano (carbonitriles), and nitro groups, on their 3- and/or 4-position(s) are presented in this review. The methods are divided mainly into intramolecular cyclizations, cycloaddition, and other methods, for example, Ugi-type reaction of β-keto acids, amines, and isonitriles, and modification of β-lactam derivatives. Cyclizations include cyclization of haloacetamidoacetates(malonates), intramolecular carbene insertion of α-diazoalkanamides, ring-opening cyclization of α,β-epoxyalkanamidoacetates, oxidative coupling of 3-oxoalkanamidoacetates, oxidative cyclization of N-p-hydroxyphenyl β-oxoalkanamides, intramolecular cyclization of aspartic acid derivatives or β-hydroxyalkanamides, and radical cyclization of N-vinyl β-oxoalkanamides. Cycloadditions incorporate Staudinger cycloaddition of ketenes and imines, cycloaddition of nitrones and alkynes, cycloaddition of nitrones and alkylidenecycopropanes and subsequent acidic rearrangement, and condensation of imines and enolates (ethers) of esters. The scope, limitation, and stereoselectivity are also discussed for some methods. Most of the β-lactam derivatives are key intermediates or precursors for preparation of β-lactam antibiotics and their analogs.     

Carbon-carbon bond formations at the benzylic positions of N-benzylxanthone imines and N-benzyldi-1-naphthyl ketone imine

Two N-benzyl imines are designed to allow for carbon-carbon bond formations at the aminated benzylic positions. Direct benzylic arylation reactions of N-benzylxanthone imine with aryl chlorides proceed under palladium catalysis in the presence of cesium hydroxide, yielding the corresponding benzhydrylamine derivatives. Alkylation reactions of N-benzyldi-1-naphthyl ketone imine with alkyl halides in the presence of potassium tert-butoxide afford the corresponding 1-phenylalkylamines in high yields. Conjugate addition of N-benzyldi-1-naphthyl ketone imine is also described.     

Mesoionic purinone analogs. VIII. Synthesis and properties of mesoionic 5-substituted-6-methylimidazo[1,2-c]pyrimidine-2,7-diones

Mesoionic imidazo[1,2-c]-pyrimidine-2,7-diones 1a-c , analogs of purine-2,8-dione, were prepared from 4-amino-l-methylpyrimidin-6-ones 6a-c . These mesoionic purinone analogs were found to exist predominantly in the C3-H tautomeric form 1 and to undergo hydrolytic ring-opening reactions to produce 2-(4-imidazol-idon-2-ylidenyl)acetamides. Reaction of 1c with dimethyl acetylene dicarboxylate produced triazacyclopent-[cd]indene 25 via 1,3-dipolar cycloaddition.     

Latent ruthenium carbene complexes with six-membered N- and S-chelate rings

New ruthenium carbene complexes with chelating N- and S-benzylidene ligands were synthesized by the reactions of second- and third-generation Grubbs catalysts with ortho-vinylbenzyl-substituted amines or sulfides. These complexes were shown to exhibit catalytic activity in ring-opening metathesis polymerization and ring-closing metathesis.     

Synthesis of nucleoside aminooxy acids

First nucleoside aminooxy acids were synthesized from furanoid sugar phthalimidooxy acids by N-glycosylation with uracil, thymine, N-benzoylcytosine, 6-N-benzoyladenine and 2-N-acetyl-6-O-diphenylcarbamoylguanine. Boc or Fmoc protected uridine aminooxy acid derivatives have also been prepared. As oxyamine protecting group, the phthalimido group was shown to be instable in MeOH, leading to the imide ring-opening product in a reversible way. This reaction was accelerated under acid or basic conditions. A uridine dimer linked by N-oxy amide has also been prepared by coupling of uridine aminooxy ester with uridine phthalimidooxy acid. These nucleoside aminooxy acids might constitute useful building blocks for the development of novel RNA mimics and conjugates with other biomolecules or reporter compounds.     

Synthesis of spirocyclopropyl γ-lactams by tandem intramolecular azetidine ring-opening/closing cascade reaction: synthetic and mechanistic aspects

The scope and limitations of a novel intramolecular azetidine ring-opening/closing cascade reaction affording spirocyclopropyl γ-lactams from azetidines in high regio- and stereoselectivity is reported. The key step of the process is a S_N2-type ring-opening of TMSOTf-activated azetidine rings by silyl ketene acetals generated by treatment with TMSOTf and TEA. This study is a very rare example of nucleophilic ring-opening of azetidines that does not require formation of quaternary azetidinium salts by N-alkylation or the use of N-electron-withdrawing groups. Application of this process to 2-azetidinone system led to a complete change in reactivity and provide 6-aza-bicyclo[3.2.0]heptane derivatives via an unprecedented Mukaiyama aldol-like reaction involving an ester acceptor and a silyl imidate.