- 4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae
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A current issue of antimicrobial therapy is the resistance to treatment with worldwide consequences. Thus, the identification of innovative targets is an intriguing challenge in the drug and development process aimed at newer antimicrobial agents. The state-of-art of anticholera therapy might comprise the reduction of the expression of cholera toxin, which could be reached through the inhibition of carbonic anhydrases expressed in Vibrio cholerae (VchCAα, VchCAβ, and VchCAγ). Therefore, we focused our interest on the exploitation of sulfonamides as VchCA inhibitors. We planned to design and synthesize new benzenesulfonamides based on our knowledge of the VchCA catalytic site. The synthesized compounds were tested thus collecting useful SAR information. From our investigation, we identified new potent VchCA inhibitors, some of them displayed high affinity toward VchCAγ class, for which few inhibitors are currently reported in literature. The best interesting VchCAγ inhibitor (S)-N-(1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)furan-2-carboxamide (40) resulted more active and selective inhibitor when compared with acetazolamide (AAZ) as well as previously reported VchCA inhibitors.
- Mancuso, Francesca,De Luca, Laura,Bucolo, Federica,Vrabel, Milan,Angeli, Andrea,Capasso, Clemente,Supuran, Claudiu T.,Gitto, Rosaria
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p. 3787 - 3794
(2021/10/20)
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- Palladium-catalyzed asymmetric decarboxylative allylation of azlactone enol carbonates: Fast access to enantioenriched α-allyl quaternary amino acids
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We report a fast protocol for the synthesis of enantioenriched quaternary 4-allyl oxazol-5-ones. The key step is a Pd-catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α-amino acids. The use of (R,R)-DACH-phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4-allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step.
- Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,De Lorenzi, Ersilia,Colombo, Lino
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p. 732 - 741
(2019/01/09)
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- GRANZYME B DIRECTED IMAGING AND THERAPY
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Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
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Page/Page column 82; 99
(2019/09/04)
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- Latent Bronsted Base Solvent-Assisted Amide Formation from Amines and Acid Chlorides
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Weakly basic amines, including even neutral amines such as nitroaniline and aminocarboxylic acids, react with acid chlorides very efficiently in N, N -dimethylacetamide (DMAC), without addition of a base, to give the corresponding amides in high yields. The role of DMAC and related solvents as latent Bronsted bases was studied in these amidation reactions. Less basic amines, such as aromatic amines, reacted with benzoyl chloride faster than more basic aliphatic amines.
- Otsuka, Rikuto,Maruhashi, Kazuo,Ohwada, Tomohiko
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supporting information
p. 2041 - 2057
(2018/05/04)
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- Dynamic Kinetic Resolution of N-Protected Amino Acid Esters via Phase-Transfer Catalytic Base Hydrolysis
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Asymmetric base hydrolysis of α-chiral esters with synthetic small-molecule catalysts is described. Quaternary ammonium salts derived from quinine were used as chiral phase-transfer catalysts to promote the base hydrolysis of N-protected amino acid hexafluoroisopropyl esters in a CHCl3/NaOH (aq) via dynamic kinetic resolution, providing the corresponding products in moderate to good yields (up to 99%) with up to 96:4 er. Experimental and computational mechanistic studies using DFT calculation and pseudotransition state (pseudo-TS) conformational search afforded a TS model accounting for the origin of the stereoselectivity. The model suggested π-stacking and H-bonding interactions play essential roles in stabilizing the TS structures.
- Yamamoto, Eiji,Wakafuji, Kodai,Furutachi, Yuho,Kobayashi, Kaoru,Kamachi, Takashi,Tokunaga, Makoto
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p. 5708 - 5713
(2018/05/30)
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- Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid
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A novel method for the synthesis of trisubstituted oxazoles via a one-pot oxazole synthesis/Suzuki–Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki–Miyaura coupling with boronic acids provided the corresponding 2,4,5-trisubstituted oxazoles in good yields.
- Yamada, Kohei,Kamimura, Naoto,Kunishima, Munetaka
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p. 1478 - 1485
(2017/08/02)
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- Isotope-labeled differential profiling of metabolites using N-benzoyloxysuccinimide derivatization coupled to liquid chromatography/high-resolution tandem mass spectrometry
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Rationale An isotopic labeling strategy based on derivatizing amine-containing metabolites has been developed using light (12C6) and heavy (13C6) N-benzoyloxysuccinimide reagents for semi-targeted metabolomic applications. Methods Differentially labeled samples were combined and analyzed simultaneously by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS) to compare relative amounts of amine-containing metabolites. The selectivity of the reaction was determined with model metabolites and was shown to also be applicable to thiol and phenol moieties. The potential for relative quantitation was evaluated in cell extracts and the method was then applied to quantify metabolic perturbations occurring in human cultured cells under normal vs. oxidative stress conditions. Results A total of 279 derivatized features were detected in HL60 cell extracts, 77 of which yielded significant concentration changes upon oxidative stress treatment. Based on accurate mass measurements and MS/MS spectral matching with reference standard solutions, 10 metabolites were clearly identified. Derivatized compounds were found to have diagnostic fragment ions from the reagent itself, as well as structurally informative ions useful for metabolite identification. Conclusions This simple derivatization reaction can be applied to the relative quantitation of amine-, thiol- and phenol-containing compounds, with improved sensitivity and chromatographic peak shapes due to the increased hydrophobicity of polar metabolites not readily amenable to reversed-phase LC/MS analysis.
- Wagner, Michel,Ohlund, Leanne B.,Shiao, Tze Chieh,Vézina, Amélie,Annabi, Borhane,Roy, René,Sleno, Lekha
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p. 1632 - 1640
(2015/11/16)
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- Some hydrazones of 2-aroylamino-3-methylbutanohydrazide: Synthesis, molecular modeling studies, and identification as stereoselective inhibitors of HIV-1
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In accordance with our antiviral drug development attempt, acylhydrazone derivatives bearing amino acid side chains were synthesized for the evaluation of their antiviral activity against various types of viruses. Among these compounds, 8S, 11S, and 12S showed anti-HIV-1 activity with a 50% inhibitory concentration (IC50) = 123.8 μM (selectivity index, SI > 3), IC50 = 12.1 μM (SI > 29), IC50 = 17.4 μM (SI > 19), respectively. Enantiomers 8 R, 11R, and 12R were inactive against the HIV-1 strain IIIB. Hydrazones 8S, 11S, and 12 S which were active against HIV-1 wild type showed no inhibition against a double mutant NNRTI-resistant strain (K103N;Y181C). Molecular docking calculations of R- and S-enantiomers of 8, 11, and 12 were performed using the hydrazone-bound novel site of HIV-1 RT. Copyright
- Tatar, Esra,Kü?ükgüzel, Ilkay,Daelemans, Dirk,Talele, Tanaji T.,Kaushik-Basu, Neerja,De Clercq, Erik,Pannecouque, Christophe
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p. 140 - 153
(2013/04/10)
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- Iodine(III)-promoted synthesis of oxazolines from N-allylamides
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PhI(OAc)2 (activated by BF3·OEt2) has been used to promote the oxidative cyclization of N-allylamides to give oxazolines. The reaction products are formed in high yield and, when a branched allylic amine is used, high diastereoselectivity. Initial mechanistic experiments suggest that the final C-O bond is formed from a reactive tight ion pair, rather than a neutral external nucleophile.
- Moon, Nicholas G.,Harned, Andrew M.
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supporting information
p. 2960 - 2963
(2013/06/27)
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- One-pot preparation of oxazol-5(4H)-ones from amino acids in aqueous solvents
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A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the TV-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.
- Fujita, Hikaru,Kunishima, Munetaka
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p. 907 - 912
(2012/08/08)
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- Synthesis, characterization, and cytotoxicity of complexes of platinum(u) with 2,2'-bipyridine and N-benzoyl-L-amino acid dianion
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Four new platinum(II) complexes (1-4) with N-benzoyl-L-amino acid and bipy were synthesized and characterized by elemental analysis, IR, UV, 1H NMR, and mass spectra. The crystal structure of 1 was determined by X-ray diffraction analysis. Cytotoxicities were measured by MTT and SRB assays. Complexes 1-4 exert cytotoxicity with selectivity against HL-60, Bel-7402, BGC-823, and KB cell lines. This suggests that amino acids and acylated groups have important effects on cytotoxicity; the cytotoxicity is also related to the species of tumor cells, but the IC50 values do not show definite correlation with the variation of amino acids and acylated groups.
- Zhang, Jinchao,Zhang, Fangfang,Wang, Liwei,Du, Jianlong,Wang, Shuxiang,Li, Shenghui
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experimental part
p. 2159 - 2169
(2012/09/07)
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- Catalytic enantioselective Steglich rearrangements using chiral N-heterocyclic carbenes
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The evaluation of a range of enantiomerically pure NHCs, prepared in situ from imidazolinium or triazolium salt precatalysts, to promote the catalytic enantioselective Steglich rearrangement of oxazolyl carbonates to their C-carboxyazlactones, is reported. Modest levels of enantioselectivity (up to 66% ee) are observed using oxazolidinone derived NHCs.
- Campbell, Craig D.,Concellon, Carmen,Smith, Andrew D.
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experimental part
p. 797 - 811
(2011/08/06)
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- Chiral relay in NHC-mediated asymmetric β-lactam synthesis II; asymmetry from NHCs derived from acyclic 1,2-diamines
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The synthesis of a range of imidazolinium salts derived from acyclic 1,2-diamines, and an evaluation of the reactivity and asymmetric induction of the corresponding NHCs as catalysts for the asymmetric synthesis of β-lactams, is reported. An N-methyl-substituted NHC derived from (1R,2R)-1,2-diphenylethanediamine shows optimal reactivity and enantioselectivity in this series, in contrast to that observed with NHCs derived from (1R,2R)-cyclohexane-1,2-diamine.
- Duguet, Nicolas,Donaldson, Adele,Leckie, Stuart M.,Kallstroem, Eddy A.,Campbell, Craig D.,Shapland, Peter,Brown, Thomas B.,Slawin, Alexandra M.Z.,Smith, Andrew D.
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experimental part
p. 601 - 616
(2010/08/20)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 51
(2010/12/31)
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- Reactivity of α-amino acids in the N-acylation with benzoic acid esters in aqueous dioxane
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The effect of the nitro group as a substituent in the phenoxide part of phenyl benzoate on the rate of N-acylation of glycine, L-proline,and L-valine in the water (40 wt %)-dioxane solvent was studied. The activation parameters of glycine reactions with the esters were measured. The existence of compensation effect and the linear relation of the logarithms of the acylation constants to the Hammett constants were revealed. The energy of the LUMO of esters can serve as the descriptors of the easters reactivity. Pleiades Publishing, Ltd., 2010.
- Ishkulova,Oparina,Kochetova,Kustova,Kalinina,Kuritsin
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experimental part
p. 964 - 967
(2011/01/07)
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- Asymmetric synthesis of α- And β-amino acids by diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl) imines
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The diastereoselective addition of triorganozincates to (R)-N-(tert-butanesulfinyl)imines has been used as a key step to achieve the synthesis of highly enantiomerically enriched N-protected α- and β-amino acids. Desulfinylation of the addition products followed by benzoylation of the nitrogen atom of the obtained primary amines and oxidation of one of the substituents on the carbon atom connected to the nitrogen complete the sequence. Using the same configuration in the sulfinyl chiral auxiliary, α-amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α- Disubstituted α-amino esters with high enantiomeric purity can also be prepared when α-imino esters are the starting substrates.
- Almansa, Raquel,Collados, Juan F.,Guijarro, David,Yus, Miguel
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experimental part
p. 1421 - 1431
(2010/11/02)
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- A new method proposed for the determination of absolute configurations of α-amino acids
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Enantiopure α-amino acids were converted to 4-substituted 2-aryl- and 2-alkyl-5(4H)-oxazolones under partial racemization. These nonracemic mixtures were dissolved in CDCl3, an equimolar amount of the chiral dirhodium complex Rh2(II)[(R)-(+)-MTPA]4 (MTPA-H = Mosher's acid) was added, and the 1H NMR spectra of the resulting samples were recorded [dirhodium method). The relative intensities of 1H signals dispersed by the formation of diastereomeric adducts allow to determine the absolute configuration (AC) of the starting a-amino acids. Binding atoms in the adducts were identified by comparing the 1H and 13C chemical shifts of the oxazolones in the absence and presence of Rh2(II)[(R)-(+)- MTPA]4. Thereby, information about the scope and limits of this method can be extracted. A protocol how to use this method is presented. Copyright
- Gomez, Edison Diaz,Duddeck, Helmut
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experimental part
p. 222 - 227
(2010/02/28)
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- Application of the addition of triorganozincates to N-(tert-butanesulfinyl)imines to the enantioselective synthesis of α-amino acids
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Highly enantiomerically enriched N-protected α-amino acids can be easily prepared from optically pure N-(tert-butanesulfinyl)imines by a four-step sequence involving: diastereoselective addition of a triorganozincate to the imine, removal of the sulfinyl group, benzoylation of the nitrogen atom of the obtained primary amine and oxidation of one of the substituents on the carbon atom α to the nitrogen. Using the same configuration in the sulfinyl chiral auxiliary, amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α-Disubstituted α-amino esters with high optical purity can also be prepared by the diastereoselective addition of trialkylzincates to α-imino esters.
- Almansa, Raquel,Guijarro, David,Yus, Miguel
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scheme or table
p. 4188 - 4190
(2009/12/01)
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- Organocatalytic asymmetric addition of alcohols and thiols to activated electrophiles: Efficient dynamic kinetic resolution and desymmetrization protocols
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(Chemical Equation Presented) Bifunctional urea-based cinchona alkaloid derivatives have been shown to promote highly efficient DKR reactions of azalactones using an alcohol nucleophile. The optimum catalyst is remarkably insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine-, and phenylalanine-derived azalactones to undergo DKR with unprecedented levels of enantioselectivity using a synthetic catalyst. The first DKR of these substrates by thiols and the highly enantioselective desymmetrization of a meso-glutaric anhydride by thiolysis are also reported.
- Peschiulli, Aldo,Quigley, Cormac,Tallon, Sean,Gun'ko, Yuri K.,Connon, Stephen J.
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p. 6409 - 6412
(2008/12/22)
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- Chiral permselectivity in nanoporous opal films surface-modified with chiral selector moieties
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The chiral permselectivity in thin opal films modified on the silica surface with chiral selector moieties was studied as a function of opal film geometry, supporting electrolyte concentration, solvent polarity, and chiral selector and linker structure. While opal film thickness, supporting electrolyte concentration and linker length and structure did not have a significant influence on the chiral permselectivity, the nanopore size, solvent polarity and selector structure had a pronounced effect. These observations are in agreement with the chiral selectivity mechanism in the opal films in which the permeating enantiomers are transported with different rates through the surface utilizing non-covalent interactions between the chiral permeant molecules and surface-bound chiral selectors. The chiral selectivity (transport rate ratio for S and R enantiomers) achieved in the present study was 4.5, which is one of the highest reported for chiral membranes. The Royal Society of Chemistry 2007.
- Cichelli, Julie,Zharov, Ilya
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p. 1870 - 1875
(2008/02/07)
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- Beauveria bassiana ATCC 7159 contains an L-specific α-amino acid benzamidase
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Biotransformation of a series of racemic N-benzoyl α-amino acids by the fungus Beauveria bassiana ATCC 7159 results in isolation of the corresponding D-amino acid benzamides in high enantiomeric purity and yield.
- Holland, Herbert L.,Andreana, Peter R.,Salehzadeh-Asl, Reza,Van Vliet, Aaron,Ihasz, Nancy J.,Brown, Frances M.
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p. 667 - 672
(2007/10/03)
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- Direct resolution of optically active isomers on chiral packings containing ergoline skeletons. 5. Enantioseparation of amino acid derivatives
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A new procedure for ergot alkaloid-based chiral stationary phase preparation is described. Synthesis is based on bonding the allyl derivative of terguride to mercaptopropylsilanized silica gel. The packing exhibits higher content of chiral selector, stability, reproducibility, and enantioselectivity toward amino acids compared to that previously studied. The chromatographic behavior of amino acids with different side chains and substituent groups is investigated in order to obtain a deeper insight into the enantiodiscriminative mechanism as well as to determine the limitations and strengths of terguride as a chiral selector for this class of compounds. A variety of factors, including mobile phase parameters such as pH, ionic strength, content and nature of organic modifier, and temperature, are examined. A new procedure for ergot alkaloid-based chiral stationary phase preparation is described. Synthesis is based on bonding the allyl derivative of terguride to mercaptopropylsilanized silica gel. The packing exhibits higher content of chiral selector, stability, reproducibility, and enantioselectivity toward amino acids compared to that previously studied. The chromatographic behavior of amino acids with different side chains and substituent groups is investigated in order to obtain a deeper insight into the enantiodiscriminative mechanism as well as to determine the limitations and strengths of terguride as a chiral selector for this class of compounds. A variety of factors, including mobile phase parameters such as pH, ionic strength, content and nature of organic modifier, and temperature, are examined.
- Messina,Girelli,Flieger,Sinibaldi,Sedmera,Cvak
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p. 1191 - 1196
(2007/10/03)
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- Coupling of N-trifluoroacetyl amino acids under 'neutral' conditions.
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The possibility of using the trifluoroacetyl group as a base-labile N-protection in peptide synthesis is discussed.Under normal coupling conditions, a very high level of racemization is observed.However, when 'neutral' coupling conditions (by silylation of amino acids or peptides) were used, the coupling racemization decreased as much as 1-2percent. - Key words: peptide coupling; N-protection; N-trifluoroacetyl amino acid; racemization, silylated amino acid
- Benouargha, Amina,Verducci, Jean,Jacquier, Robert
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p. 824 - 828
(2007/10/02)
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- Enzymatic Asymmetric Synthesis of α-Amino Acids. Enantioselective Cleavage of 4-Substituted Oxazolin-5-ones and Thiazolin-5-ones
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A general enzymatic asymmetric synthesis of L-α-amino acids has been developed.This method entails the use of the Pseudomonas cepacia lipase (P-30) to catalyze the enantioselective methanolysis of a variety of 4-substituted 2-phenyloxazolin-5-one derivatives in a nonpolar organic solvent to furnish optically active N-benzoyl-L-α-amino acid methyl esters (ee = 66-98 percent), which in turn is subjected to a protease-catalyzed kinetic resolution yielding enantiomerically pure N-benzoyl-L-α-amino acids.This synergistic coupling of two enzymes allows the ready preparation of L-α-amino acids of high enantiopurity in yields greater than 50 percent, an inherent advantage over conventional resolution procedures.Two proteases were found to catalyze the enantioselective hydrolysis of a variety of 4-substituted 2-phenylthiazolin-5-one derivatives to give N-(thiobenzoyl)-L-α-amino acids of high optical purity.
- Crich, Joyce Z.,Brieva, Rosario,Marquart, Peer,Gu, Rui-Lin,Flemming, Steffen,Sih, Charles J.
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p. 3252 - 3258
(2007/10/02)
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- Imidazole analogs of mevalonolactone and derivatives thereof for use in inhibiting cholesterol biosynthesis and lowering blood cholesterol level
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Compounds of the formula STR1 and the pharmaceutically acceptable acid addition salts thereof, wherein the various substituents are defined hereinbelow and the use thereof for inhibiting cholesterol biosynthesis and lowering the blood cholesterol level and, therefore, in the treatment of hyperlipoproteinemia and atherosclerosis, pharmaceutical compositions comprising such compounds and processes for and intermediates in the synthesis of such compounds.
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- Intermediate imidazole acrolein analogs
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Compounds of the formula STR1 and the pharmaceutically acceptable acid addition salts thereof, wherein the various substituents are defined hereinbelow, the use thereof for inhibiting cholesterol biosynthesis and lowering the blood cholesterol level and, therefore, in the treatment of hyperlipoproteinemia and atherosclerosis, pharmaceutical compositions comprising such compounds and processes for and intermediates in the synthesis of such compounds.
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