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ABSTRACT: Although 1,2-cyclic sulfamidates derived from α-methylisoserine undergo nucleophilic displacement at the quaternary center, to the best of our knowledge their behavior with amines as nucleophiles has never been explored. We have found that a broad range of amines can be used, demonstrating the scope of the reaction, and that excellent control of the chemoselectivity can be achieved. Application of this methodology for the synthesis of a chiral α,β-diamino acid and an important piperazinone heterocycle is also presented. Additionally, we have found that DMF and DMSO behave not only as polar aprotic solvents but also as O-nucleophilic reagents, allowing the incorporation of an oxygen atom at a quaternary center of the electrophile, with inversion of configuration.
Chemistry 04/2013; · 5.93 Impact Factor
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ABSTRACT: There are many conventional microbiological methods in routine clinical practice to determine the sensitivity of common bacteria. The problem with these methods arises with bacteria that do not grow on habitual media (Rickettsia spp., Coxiella spp. and Anaplasma spp., among others) and for which there are no standardized techniques to determine their antimicrobial susceptibility. In addition, the techniques that are used for the culture of these fastidious bacteria show problems in both accuracy and reproducibility and, in some cases, the in vitro antimicrobial susceptibility of bacteria shows poor correlation with therapeutic outcome. Therefore, it becomes difficult to determine the antimicrobial drug susceptibility of some bacteria and, thus, to assess the therapeutic effect of drugs. The scientific breakthroughs that have taken place in recent years have allowed the use of new techniques that facilitate and improve microbiological study. This paper reviews the use of nuclear magnetic resonance spectroscopy as an alternative tool for determining antimicrobial drug susceptibility.
Future Microbiology 04/2013; 8:537-547. · 3.82 Impact Factor
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ABSTRACT: Using olefin metathesis as a key step, four neoglycoconjugates incorporating α-O-glucose, α-S-glucose or β-S-glucose as a carbohydrate unit and l-serine or l-cysteine as an amino acid moiety have been synthesized. The four-atom carbon spacer allows the carbohydrate to explore a wide-ranging conformational space, which may have important implications for the molecular recognition of these molecules.
Carbohydrate research 03/2013; 373C:1-8. · 2.03 Impact Factor
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ABSTRACT: The reactions of cyclic sulfamidates as electrophiles with a variety of nitrogen-containing aromatic heterocycle nucleophiles, such as pyridines, N-alkylimidazoles and N-methylbenzimidazol, was explored. In all cases, although the nucleophilic substitution reactions occurred on quaternary centres, elimination products were not detected. The inversion of configuration at this quaternary centre was determined by X-ray diffraction analysis and the enantiomeric excess of the reactions was checked by chiral HPLC. This synthetic approach allowed us to obtain a new family of chiral charged β(2,2) -amino acids, including a new bisamino acid that incorporates an imidazolium salt as a cross-linker. In this context, the treatment of these chiral imidazolium salts with Ag(2) O opens the way to new chiral N-heterocyclic carbenes, which are important substrates in the fields of organometallic and organocatalytic chemistry. Additionally, we have done a thorough conformational analysis of these β-amino acid derivatives, both in the solid state and in solution. The most important conformational feature of these acyclic systems is the rigidity of the N-CH(2) -C-N(+) dihedral angle, which is essentially due to the gauche effect.
Chemistry 10/2012; · 5.93 Impact Factor
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ABSTRACT: In this study, La Rioja wine terroir was investigated by the use of (1)H NMR metabolomics on must and wine samples. Rioja is a small wine region in central northern Spain which can geographically be divided into three subareas (Rioja Alta, Rioja Baja, and Rioja Alavesa). The winemaking process from must, through alcoholic and malolactic fermentation, was followed by NMR metabolomics and chemometrics of nine wineries in the Rioja subareas (terroirs). Application of interval extended canonical variate analysis (iECVA) showed discriminative power between wineries which are geographically very close. Isopentanol and isobutanol compounds were found to be key biomarkers for this differentiation.
Journal of Agricultural and Food Chemistry 03/2012; 60(13):3452-61. · 2.82 Impact Factor
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ABSTRACT: The asymmetric sulfa-Michael additions of appropriately protected L- and D-cysteine derivatives to new chiral dehydroamino acid derivatives have been developed as key steps in the synthesis of biologically important cysteine derivatives, such as lanthionine (Lan) and β-methyllanthionine (MeLan), which are unusual bis-α-amino acids found in the emerging lantibiotics such as nisin.
Organic Letters 12/2011; 14(1):334-7. · 5.86 Impact Factor
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ABSTRACT: A domino process that involves a Michael-type addition followed by a Dieckmann reaction mediated by the participation of the cyclic carbamate group is the key step in the synthesis of both enantiomers of α-(hydroxymethyl)glutamic acid (HMG).
The Journal of Organic Chemistry 08/2011; 76(17):6990-6. · 4.45 Impact Factor
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ABSTRACT: This paper explores the role of a hindered cyclic sulfamidate derived from α-methylisoserine as an electrophile in a nucleophilic displacement reaction with nitrogen-containing aromatic heterocycles. Several imidazoles and pyrazole were tested as nucleophiles in the absence of an additional base to give the corresponding ring-opening compounds. We show that the process takes place by inversion of the configuration of the quaternary electrophilic center, retaining the enantiomeric excess of the starting sulfamidate. This reaction opens the way to obtain important quaternary imidazole derivatives such as an innovative type of bis-amino acid related to histidinoalanine and a novel α,α-disubstituted β-amino acid (β(2,2)-amino acid).
The Journal of Organic Chemistry 05/2011; 76(10):4034-42. · 4.45 Impact Factor
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ABSTRACT: Several metathesis sequences have been carried out using 7-azanorbornenes as starting materials. The occurrence of several exocyclic olefin patterns in the bridgehead position of this system opens the way to gain interesting spirocyclic compounds, which were achieved using several ring-rearrangement metatheses (RRM). The metathesis products, thus obtained, may be useful for the synthesis of new peptidomimetics and related compounds.
The Journal of Organic Chemistry 04/2011; 76(9):3381-91. · 4.45 Impact Factor
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Francisco Corzana,
Jesús H Busto,
Filipa Marcelo,
Marisa García de Luis,
Juan L Asensio,
Sonsoles Martín-Santamaría,
Yolanda Sáenz,
Carmen Torres,
Jesús Jiménez-Barbero,
Alberto Avenoza, Jesús M Peregrina
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ABSTRACT: A novel Tn antigen mimic, in which the natural underlying amino acid has been replaced by the non-natural α-methylserine analogue, is reported. This derivative exhibits a similar affinity for a natural lectin as for the natural Tn and retains the bioactive conformation observed in the Tn-containing glycopeptides with anti-MUC1 antibodies.
Chemical Communications 03/2011; 47(18):5319-21. · 6.17 Impact Factor
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ABSTRACT: The ties that bind: The incorporation of non-natural residues in the peptide backbone allows the design of O-glycosylation points in helical segments. This strategy could help to modulate the binding properties between glycopeptides and their protein receptors, such as lectins and antibodies.
Chemistry 02/2011; 17(11):3105-10. · 5.93 Impact Factor
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ABSTRACT: The binding properties of different carbohydrates and glycopeptides containing the β-O-2-deoxy-2-(N-acetyl)-D-glucosaminyl (β-O-GlcNAc) to a synthetically prepared lectin-like receptor have been analyzed. The study combines the use of NMR spectroscopy experiments with extensive MD simulations in explicit water. Notably, the presence of a key hydrogen bond between the receptor and the OMe group of the β-O-GlcNAc-OMe derivative appears to be responsible for the high selectivity observed for this compound. In addition, to study the effect on the binding of the underlying amino acid, we have prepared different model glycopeptides, which include the non-natural α-methylserine and α-methylthreonine as underlying amino acids. Interestingly, the presence of a methyl group decreases the affinity constant, especially in those cases in which a β-methyl group is present. As a result, the serine-containing glycopeptide exhibited the highest affinity constant of the glycopeptides, and the threonine derivative showed the lowest one. This low selectivity could have its origin in the difficulty to form both specific hydrogen bonds and hydrophobic (CH-π) contacts.
ChemBioChem 01/2011; 12(1):110-7. · 3.94 Impact Factor
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Annalen der Chemie und Pharmacie 05/2010; 2010(18):3525 - 3532. · 3.10 Impact Factor
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ABSTRACT: Because the metabolite transformations in wine fermentation processes play a crucial role in the organoleptic and hygienic quality of wines, the nuclear magnetic resonance (NMR) technique is presented as a significant tool to follow metabolic pathways. In this paper, we investigated the transformation of several amino acids into their corresponding higher alcohols during the alcoholic fermentation, showing that the amino acids are totally consumed in the first stages of the process.
Journal of Agricultural and Food Chemistry 04/2010; 58(8):4923-7. · 2.82 Impact Factor
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ABSTRACT: The synthesis and conformational analysis of a new type of conformationally restricted alpha-amino acid analogue of the amino acid antibiotic furanomycin is presented. The restriction involves the cis-fused cyclobutane and tetrahydrofuran units, generating the unusual 2-oxabicyclo[3.2.0]heptane core, which is found in a great number of biologically active natural products. The synthetic strategy is based on a formal [2 + 2] cycloaddition between 2-(acylamino)acrylates as acceptor alkenes and 2,3-dihydrofuran as a donor alkene, promoted by bulky aluminum-derived Lewis acids, particularly by methylaluminoxane (MAO). Additionally, following the same strategy, the synthesis of furanomycin analogues incorporating the 2-oxabicyclo[4.2.0]octane is reported.
The Journal of Organic Chemistry 02/2010; 75(3):545-52. · 4.45 Impact Factor
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ABSTRACT: The synthesis and the conformational analysis in aqueous solution of a peptide and a glycopeptide containing the sequence threonine-alanine-alanine (Thr-Ala-Ala) are reported. Furthermore, the threonine residue has been replaced by the quaternary amino acid alpha-methylserine (MeSer) and their corresponding non-natural peptide and glycopeptide are also studied. The conformational analysis in aqueous solution combines NOEs and coupling constants data with Molecular Dynamics (MD) simulations with time-averaged restraints. The study reveals that the beta-O-glycosylation produces a remarkable and completely different effect on the backbone of the peptide derived from Thr and MeSer. In the former, the beta-O-glycosylation is responsible for the experimentally observed shift from extended conformations (peptide) to folded ones (glycopeptide). In contrast, the beta-O-glycosylation of the MeSer-containing peptide, which clearly shows two main conformations in aqueous solution [extended ones (70%) and beta-turn (30%)], causes a high degree of flexibility for the backbone.
The Journal of Organic Chemistry 11/2009; 74(24):9305-13. · 4.45 Impact Factor
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ABSTRACT: Cyclic hindered sulfamidates exhibited an outstanding performance in their ring-opening reactions with alcohols and in the absence of any external activator. The mechanism of this unprecedented transformation was thoroughly studied both experimentally and theoretically. As a result, a nontrivial stepwise pathway involving solvent-induced conversion of the sulfamidates to activated aziridinium and then to oxazolinium cations, which are finally opened at their 5-position with inversion of configuration, is proposed. The presence of the SO(3) moiety in the sulfamidate was revealed as a "built-in activator". In fact, the spontaneous SO(3) cleavage takes place under the reaction conditions and avoids the subsequent step of hydrolysis after the ring opening of the sulfamidates. This is another important improvement of this methodology with respect to the standard basic conditions, allowing a greater compatibility with other functional groups. Furthermore, the carbamate group plays a key role in this mechanism. Briefly, a highly chemoselective and stereoespecific formal solvolysis of hindered sulfamidates with alcohols without further activation is described. This reaction takes place exclusively at the quaternary center with inversion of configuration, providing a new straightforward synthetic route to O-substituted alpha-methylisoserines.
Chemistry 09/2009; 15(38):9810-23. · 5.93 Impact Factor
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ABSTRACT: The synthesis and the conformational study in the solid state and in aqueous solution of a peptide and a glucopeptide containing the non-natural (1S,2S)-1-amino-2-hydroxycyclobutanecarboxylic acid (c(4)Ser) residue are reported. This is the first example of a glycopeptide containing a carbohydrate moiety linked to an underlying non-natural amino acid residue. The conformational analysis in solution combines NOEs and coupling constants data with Molecular Dynamics (MD) simulations with time-averaged restraints. The study reveals that the c(4)Ser-Ala-Ala diamide peptide shows a conformation of two consecutive beta-turn type III structures (the basic structural element of a 3(10) helix). However, none of the turns observed in the peptide are present in the derived glucopeptide. The influence of the carbohydrate moiety on the peptide backbone can be explained by means of the existence of two simultaneous hydrogen bonds, between the endocyclic oxygen of the glucose and two amidic protons of the peptide. In addition, the non-natural residue favors the existence of an unusual high energy conformation for the glycosidic linkage, the so-called anti-phi conformation.
Organic & Biomolecular Chemistry 08/2009; 7(14):2885-93. · 3.70 Impact Factor
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Chemistry 07/2009; 15(30):7297-301. · 5.93 Impact Factor
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ABSTRACT: In this study, we focused our attention on monitoring the levels of important metabolites of wine during the alcoholic and malolactic fermentation processes by quantitative nuclear magnetic resonance (qNMR). Therefore, using (1)H NMR, the method allows the simultaneous quantification of ethanol, acetic, malic, lactic, and succinic acids, and the amino acids proline and alanine, besides the ratio proline/arginine through fermentation of must of grapes corresponding to the Tempranillo variety. Each (1)H NMR spectrum gives direct and visual information concerning these metabolites, and the effectiveness of each process was assessed and compared by carrying out analyses using infrared spectroscopy to ethanol and acetic acid. The quantitative data were explained with the aid of chemometric algorithms.
Journal of Agricultural and Food Chemistry 04/2009; 57(6):2112-8. · 2.82 Impact Factor
