Influence of amino acid sequence on the interaction of short peptides containing 3-[2-(9-anthryl)benzoxazol-5-yl]-alanine with β-cyclodextrin

The influence of peptide sequence and Leu chirality in linear and cyclic peptides containing 3-[2-(9-anthryl)benzoxazol-5-yl]alanine on interaction with β-cyclodextrin were studied using fluorescence and NMR spectroscopy. The analysis of enthalpy-entropy compensation effect (α=1.05±0.02 and TΔS₀ ⁰=15.1±0.5 kJ mol^?1) indicates that the entropic contribution connected with the solvent reorganization is the major factor governing the peptides-β-cyclodextrin complexation. Moreover, spatial orientation of guest-host molecule depends more than association constant on Leu residue configuration. However, the cyclization of the peptide chain substantially decrease the association constant with β-CD. An analysis of 2D NMR spectra reveals that inclusion complex is formed by penetration of cyclodextrin cavity from wider and narrow rims by anthryl group in the case of Box(Ant)-SPKL or anthryl and Leu residues for Box(Ant)-SPK(D)L analogue.      

A Synthesis of novel IH-Imidazo[1,2-α]Indole-3-Carboxylates

A route to the uncommon imidazo[1,2-α]indole nucleus 1 is described via functionalisation and annelation of readily accessible 2-amino-indole-3-carboxylates 5. Intramolecular cyclization of a key 2-indolylformamidate 6 was utilised for the preparation of the 3,9-diester intermediates 7.     

Synthesis of novel non-natural spiro[2.3]hexane amino acids,the conformationally restricted analogs of γ-aminobutyric acid

3-Methylenecyclobutanecarboxylic acid and its methyl ester were used as the starting compounds for the synthesis of new spiro[2.3]hexane amino acids, the conformationally rigid analogs of γ-aminobutyric acid, namely, 5-aminospiro[2.3]hexanecarboxylic and 5-amino-spiro[2.3]hexanephosphonic acids, promising modulators of GABAergic cascades in the human central nervous system. The methods developed for the synthesis of the target amino acids are based on the reactions of catalytic [1+2] cycloaddition of diazoacetic and diazophosphonic esters to 3-substituted methylenecyclobutanes, as well as on a modified Curtius reaction for the transformation of a carboxy group to the amine one.     

Does amino acid sequence determine the properties of Aβ dimer?

The effect of random reshuffling of amino acids on the properties of dimers formed by Aβ peptides is studied using replica exchange molecular dynamics and united atom implicit solvent model. We show that thermodynamics of dimer assembly and the dimer globule-like state are not affected by sequence permutation. Furthermore, sequence reshuffling does not change the distributions of non-local interactions and, to a large extent, amino acids in the dimer volume. To rationalize these results, we demonstrate that Gaussian statistics applies surprisingly well to the end-to-end distances of the peptides in the dimer implying that non-bonded interactions between distant along the chain amino acids are effectively screened. This observation suggests that peptides in the dimer behave as ideal chains in polymer melt, in which amino acids lose their "identity" and therefore the memory of sequence position. As a result large-scale properties of the dimer become universal or sequence independent. Comparison of our simulations with the prior theoretical studies and their implications for experiments are discussed.     

Synthesis of New Pyrazolo[1,5-α]quinazoline Derivatives

The reaction of various anthranilic acid derivatives or their esters with 4-oxotetrahydrothiophene-3-carbonitrile 2, 2-oxocyclopentanecarbonitrile (9, n = 1) or 2-oxocyclohexanecarbonitrile (9, n = 2) in ethanol under reflux conditions giving rise the formation of single products isolated in each case after simple filtration. The products were characterized as pyrazolo[1,5-a]quinazolin-5-ones 4 instead of the expected pyrazol-3-amines 3. These cascade condensation–intramolecular acylation processes generated in one-step reactions from simple starting materials novel heterocyclic scaffolds ready for further functionalization. The present synthetic protocol provides acceptable yields of new tetracyclic products in high purity.     

Synthesis of some sulfur-containing pyrido[1,2-α]pyrimidines

4-Methylthiopyrido[1,2-α]pyrimidin-2-one and 2-hydroxypyrido[1,2-α]pyrimidine-4-thione derivatives were synthesized by the addition ofN-(4-R-pyrid-2-yl)acetoacetamides (R = H, Me) to CS₂ under phase-transfer conditions followed by the alkylation of the reaction products with Mel. The molecular structure of 3-acetyl-4-methylthiopyrido[1,2-α]pyrimidin-2-one is established by X-ray analysis.     

An Improved Synthesis of 2-Chlorinated Imidazo[1,2-α]-pyridines and the Application of this Procedure for the Synthesis of Several New Polychlorinated Imidazo[1,2-α]Pyridnes.

Polychlorinated imidazo[1,2-α]pyridines were synthesized as analogs of certain chlorinated benzimidazoles. The imidazo[1,2-α]pyridines were obtained by a condensation of ethyl bromoacetate and chlorinated 2-aminopyridines. These condensation products were treated with an ion exchange resin to effect an exchange of hydrobromide salts with hydrochloride salts. These compounds were subsequently treated with POCl₃ to convert the imidazo[1,2-α]pyridin-2-ones into 2-chloroimidazo[1,2-a]pyridines.     

A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives

α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S₅-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.     

Synthesis of the 3-0, 4-0 and 6-0 Sulfates of Methyl 2-amino-2-deoxy-α-D-Glucopyranoside

Abstract

Starting with methyl 2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (1), the isomeric methyl 2-amino-2-deoxy-α-D-glucopyranoside 3-, 4-, and 6-sulfates have each been prepared by sulfation of suitably blocked intermediates. Tritylation and acetylation of 1 followed by detritylation gave methyl 3,4-di-0-acetyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (3), having a free 6-hydroxyl group. Base catalyzed 0–4→0–6 acetyl migration provided the corresponding 3,6 di-O-acetyl derivative (4) posessing a free 4-hydroxyl group. Preparation of methyl 4,6-0-benzylidene-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside (9) provided the intermediate bearing a free 3-hydroxyl group. 0-sulfation of 3, 4, and 9 was effected with the pyridine sulfur trioxide complex in dry pyridine.     

Synthesis of 1-functionalized imidazo[1,5-а]pyrazolo[5,1-с]pyrazines

Chemistry of Heterocyclic Compounds - 4-Chloropyrazolo[1,5-a]pyrazines react with ethyl isocyanoacetate to form ethyl imidazo[1,5-a]pyrazolo[5,1-c]pyrazine-1-carboxylates, hydrolysis of which...     

Application of [3 + 2]-Cycloaddition in the Synthesis of Valdecoxib

A large scale synthesis of valdecoxib 1 is described. Our work features potential application of [3 + 2]-dipolar cycloaddition involving enamine and in situ–generated nitrile oxide derivatives.     

New Approach to Synthesis of Tetrahydroisoquino[2,1-c] [1,3]benzodiazepine

A concise and efficient synthesis of the new compounds tetrahydroisoquino [2,1-c] [1,3]benzodiazepine 5 and 7 is reported.     

1.3λ3-Azaphospholo[1.2-α]pyridine - 1.2.4.λ3-diazaphospholo[1.5-α]pyridine - 1.3λ3-azaarsolo[1.5-α]pyridine - 1.2.4λ3-diazaarsolo[1.5-α]pyridine

The title compounds are prepared by reaction of 1.3-oxazolo[13.2-α]pyridinium- and 1.3.4-oxadiazolo[3.2-α]pyridiniumsalts with P(SiMe₃)₃, resp. As(SiMe₃)₃.     

Synthesis of spiro[isoquinoline-4,4′-pyran]-3-imines

A method has been developed for the synthesis of 4-[2-(bromomethyl)phenyl] tetrahydro-2H-4-pyrancarbonitrile and a study was carried out on the reaction of this compound with primary amines, which, depending on the conditions, leads to either 4-[2-(R-aminomethyl)phenyl]tetrahydro-2H-4-pyrancarbonitriles or hydrobromides of 2-R-aryl-2,3,2,3,5,6-hexahydrospiro[isoquinoline-4(1H),4-pyran]-3-imines.Taras Shevchenko Kiev University, 252017 Kiev, Ukraine; e-mail: vkysil@mail.univ.kiev.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1035–1041, August, 2000.     

Synthesis ofα-D-GlcpNAc-（1→2）-[α-D-ManpNAc-（1→3）-]α-L-Rhap-（1→2）-α-L-Rhap-（1→3）-α-L-Rhap,the repeating unit of O10 antigen from Acinetobacter baumannii

An efficient synthesis ofα-D-GlcpNAc-（1→2）-[α-D-ManpNAc-（1→3）-]α-L-Rhap-（1→2）-α-L-Rhap-（1→3）-α-L-Rhap（1）, the repeating unit of the O10 antigen from Acinetobacter baumannii was achieved via sequential assembly of the building blocks,p- methoxylphenyl 2,4-di-O-benzoyl-α-L-rhamnopyranoside（2）;2-O-allyloxycarbonyl-3,4-di-O-bcnzoyl-α-L-rhamnopyranosyl tri- chloroacetimidate（3）;4-methoxylphenyl 3-O-allyloxycarbonyl-4-O-benzoyl-α-L-rhanmopyranoside（4）;2-azido-3-O-benzoyl-2- deoxy-4,6-O-isopropylidene-α-D-mannopyranosyl trichloroacetirnidatc（5）;2-azido-3,4,6-tri-O-benzoyl-2-deoxy-α,β-D-glucopyr- ano syl trichloroacetimidatc（6）.The total yield of 1 from 4 was 4.7%.     

Synthesis of novel β2,2-amino acid from D-mannose and attempted synthesis of peptides from the amino acid

The study describes the synthesis of new α,α-disubstituted β-amino acid (β^2,2-Caa) and attempts the synthesis of peptides from it. The β^2,2-Caa was prepared from D-(+)-mannose, using crossed aldol and Cannizzaro reactions.     

Synthesis and antitumor activity of some new pyrazolo[1,5-α]pyrimidines

New series of pyrazolo[1,5-α]pyrimidine derivatives 7a-i,11a-c and Schiff bases 13a-c were synthesized and screened for their in vitro antitumor activity against three human carcinoma cell lines,namely colorectal carcinoma(HCT116),prostate adenocarcinoma(PC-3) and liver carcinoma(HepG-2) using MTT cytotoxicity assay at 100 μg/mL.Some of the tested compounds displayed good anticancer activities against HCT-116 and PC-3 cells.Whereas,compounds 7d and 11 a showed better antitumor activity than the rest of the compounds against both cell lines.A structure-activity relationship(SAR) has been discussed and structures of the newly synthesized compounds were confirmed by different spectral data(MS,IR,~1H NMR and ~(13)C NMR) and elemental analysis.     

Studies on the Cyclisation of 4-[2′-Cyclohexenyl]-3-hydroxy[1]benzopyran-2-one

The bicyclic coumarin derivative-1, 3 propano-2-bromo-1,2-dihydro-3H-pyrano [2, 3-c] [1]benzo-pyran-5-one (8) was synthesised by a sequence of reaction viz. acetylation of 4-[2′-cyclohexenyl] -3-hydroxy [1] benzopyran-2-one (4), addition of bromine to cyclohexenyl double bond and treating the resulting acetyldi-bromo derivative (7) with 4% alcoholic KOH. Benzofuro [2, 3-c] [1] -benzopyran-6-one (10) was synthesised from 4 via oxymercuration with mercuric acetate in methanol followed by dehydrogenative damercuration with Pd-C in refluxing diphenyl ether.     

Synthesis of 3-[tris(ψ-trifluoropropyl)sily]propyldimethylsilane

Monofunctional silane containing a tris(ψ-trifluoropropyl) fragment was synthesized in high yield by a series of successive reactions including the Grignard reaction, hydrosilylation, and reduction. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 808–809, April, 1999.     

Synthesis and Structure Characterization of N-Phenyl-（2S）-hydroxy-3-[（2-hydroxybenzylidene）amino]propionamide

1 INTRODUCTION Schiff bases can be conveniently prepared from the corresponding aldehyde and primary amine, which, as multidentate ligands, have already received great attention. Many metal complexes of this kind of ligands have been used successfully in various re- actions, such as Diels-Alder and hetero-Diels-Alder reactions[1], kinetic resolution of racemic epoxides[2], and Nozaki-Hiyama-Kishi (NHK) reaction[3]. Recen- tly Berkessel et al. have reported that the Cr- complex of sal…