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1.
J Chem Phys ; 160(21)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38842492

RESUMO

Both sugars and lipids are important biomolecular building blocks with exceptional conformational flexibility and adaptability to their environment. Glycolipids bring together these two molecular components in the same assembly and combine the complexity of their conformational landscapes. In the present study, we have used selective double resonance vibrational spectroscopy, in combination with a computational approach, to explore the conformational preferences of two glycolipid models (3-0-acyl catechol and guaiacol α-D-glucopyranosides), either fully isolated in the gas phase or controlled interaction with a single water molecule. We could identify the preferred conformation and structures of the isolated and micro-hydrated species and evidence of the presence of a strong water pocket, which may influence the conformational flexibility of such systems, even in less controlled environments.

2.
Org Biomol Chem ; 20(9): 1974-1981, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35179161

RESUMO

Trehalose-based probes are useful tools that allow the detection of the mycomembrane of mycobacteria through the metabolic labeling approach. Trehalose analogues conjugated to fluorescent probes can be used, and other probes are functionalized with a bioorthogonal chemical reporter for a two-step labeling approach. The synthesis of such trehalose-based probes mainly relies on the desymmetrization of natural trehalose using a large number of regioselective protection-deprotection steps to differentiate the eight hydroxyl groups. Herein, in order to avoid these time-consuming steps, we reinvestigated our previously reported tandem protocol mediated by FeCl3·6H2O, with the aim of modifying the ratio of the products to allow the challenging desymmetrization of the C2-symmetrical disaccharide trehalose. We demonstrate the usefulness of this method in providing easy access to trehalose analogues with a bioorthogonal moiety or a fluorophore in C-2, and also present their use in a one-step and two-step labeling approach, either of which can be used to study the mycomembrane in live mycobacteria.


Assuntos
Antibacterianos/farmacologia , Membrana Celular/efeitos dos fármacos , Cloretos/farmacologia , Corynebacterium/efeitos dos fármacos , Compostos Férricos/farmacologia , Trealose/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Cloretos/química , Compostos Férricos/química , Testes de Sensibilidade Microbiana , Trealose/síntese química , Trealose/química
3.
Chemistry ; 27(16): 5230-5239, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33433914

RESUMO

We give a full account of the total synthesis of tiacumicin B (Tcn-B), a natural glycosylated macrolide with remarkable antibiotic properties. Our strategy is based on our experience with the synthesis of the tiacumicin B aglycone and on unique 1,2-cis-glycosylation steps. We used sulfoxide anomeric leaving-groups in combination with a remote 3-O-picoloyl group on the donors that allowed highly ß-selective rhamnosylation and noviosylation that rely on H-bond-mediated aglycone delivery. The rhamnosylated C1-C3 fragment was anchored to the C4-C19 aglycone fragment by a Suzuki-Miyaura cross-coupling. Ring-size-selective Shiina macrolactonization provided a semiglycosylated aglycone that was engaged directly in the noviolysation step with a virtually total ß-selectivity. Finally, a novel deprotection method was devised for the removal of a 2-naphthylmethyl ether on a phenol, and efficient removal of all the protecting groups provided synthetic tiacumicin B.

4.
Org Biomol Chem ; 19(19): 4285-4291, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33885694

RESUMO

The synthesis of glycopyranosyl nucleosides modified in the sugar moiety has been less frequently explored, notably because of the lack of a reliable method to glycosylate pyrimidine bases. Herein we report a solution in the context of the synthesis of peptidonucleosides. They were obtained after glycosylation of different pyrimidine nucleobases with glucopyranosyl donors carrying an azide group at the C4 position. A methodological study involving different anomeric leaving groups (acetate, phenylsulfoxide and ortho-hexynylbenzoate) showed that a sulfoxide donor in combination with trimethylsilyl triflate as the promoter led to the best yields.


Assuntos
Nucleosídeos
5.
Angew Chem Int Ed Engl ; 59(16): 6612-6616, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32003915

RESUMO

A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen-bond-mediated aglycone delivery (HAD). This new HAD variant permitted highly ß-selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1-C3 fragment thus obtained was anchored to the C4-C19 aglycone fragment by adapting the Suzuki-Miyaura cross-coupling used for the aglycone synthesis. Ring-size-selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total ß selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.


Assuntos
Fidaxomicina/síntese química , Antibacterianos/síntese química , Antibacterianos/química , Catálise , Complexos de Coordenação/química , Fidaxomicina/química , Glicosilação , Ligação de Hidrogênio , Lactonas/química
6.
J Org Chem ; 83(2): 921-929, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29260550

RESUMO

Our study of the synthesis of the aglycone of tiacumicin B is discussed here. We imagined two possible strategies featuring a main retrosynthetic disconnection between C13 and C14. The first strategy was based on Suzuki-Miyaura cross-coupling of 1,1-dichloro-1-alkenes, but the failure of this pathway led us to use a Pd/Cu-dual-catalyzed cross-coupling of alkynes with allenes that had never been implemented before in a total synthesis context. We used density functional theory calculations to guide our strategic choices concerning a [2.3]-Wittig rearrangement step and the final ring-size selective Yamaguchi macrolactonization. This led to two syntheses of the aglycone of tiacumicin B, with one of last generation delivering ultimately an adequately protected and glycosylation-ready aglycone.

7.
Org Biomol Chem ; 16(2): 325-335, 2018 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-29260828

RESUMO

The activation of aryl glycosyl sulfone donors has been achieved using scandium(iii) triflate and has led to the selective preparation of α-mannosides resulting from a post-glycosylation anomerization.

8.
Chemphyschem ; 18(19): 2812-2823, 2017 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-28547843

RESUMO

The fragmentation mechanisms of prototypical disaccharides have been studied herein by coupling tandem mass spectrometry (MS) with collisional chemical dynamics simulations. These calculations were performed by explicitly considering the collisions between the protonated sugar and the neutral target gas, which led to an ensemble of trajectories for each system, from which it was possible to obtain reaction products and mechanisms without pre-imposing them. The ß-aminoethyl and aminopropyl derivatives of cellobiose, maltose, and gentiobiose were studied to observe differences in both the stereochemistry and the location of the glycosidic linkage. Chemical dynamics simulations of MS/MS and MS/MS/MS were used to suggest some primary and secondary fragmentation mechanisms for some experimentally observed product ions. These simulations provided some new insights into the fundamentals of the unimolecular dissociation of protonated sugars under collisional induced dissociation conditions.


Assuntos
Dissacarídeos/química , Simulação de Dinâmica Molecular , Prótons , Configuração de Carboidratos , Espectrometria de Massas em Tandem
9.
Org Biomol Chem ; 15(37): 7802-7812, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28876013

RESUMO

Lipo-chitotetrasaccharide analogues where one central GlcNAc residue was replaced by a triazole unit have been synthesized from a derivative obtained by chitin depolymerization and a functionalized N-acetyl-glucosamine via the copper-catalyzed azide-alkyne cycloaddition. Their evaluation in a binding assay using LYR3, a putative lipo-chitooligosaccharide receptor in Medicago truncatula, shows a complete loss of binding.


Assuntos
Quitina/análogos & derivados , Medicago truncatula/química , Proteínas de Plantas/química , Quitina/síntese química , Quitina/química , Quitosana , Oligossacarídeos
10.
Chemistry ; 20(38): 12133-43, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25098669

RESUMO

One-step assembly of hexahydroisoindole scaffolds by a sequence that combines the Petasis (borono-Mannich) and Diels-Alder reactions is described. The unique selectivity observed experimentally was confirmed by quantum calculations. The current method is applicable to a broad range of substrates, including free sugars, and holds significant potential to efficiently and stereoselectively build new heterocyclic structures. This easy and fast entry to functionalized polycyclic compounds can be pursued by further transformations, for example, additional ring closure by a cross-metathesis/Michael addition domino sequence.


Assuntos
Aldeídos/química , Reação de Cicloadição/métodos , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo
11.
Angew Chem Int Ed Engl ; 53(24): 6184-7, 2014 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-24764235

RESUMO

The umpolung of glycals with samarium diiodide offers a simple route to novel carbohydrate-derived nucleophilic reagents in a single step using a readily available reductant. The corresponding allyl samarium reagent that arises from the hexose series reacts with ketones at the C3 position with high stereoselectivity; carbon-carbon bond formation takes place only anti to the substituent at the C4 position of the dihydropyran ring. For the sialic acid series, the completely regio- and stereoselective coupling process of the samarium reagent occurs at the anomeric carbon atom and provides a new approach to the α-C-glycosides of N-acetyl neuraminic acid.


Assuntos
Iodetos/química , Samário/química , Ácidos Siálicos/química , Estrutura Molecular
12.
Angew Chem Int Ed Engl ; 53(44): 11912-6, 2014 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-25212734

RESUMO

The direct and chemoselective N-transacylation of peracetylated chitooligosaccharides (COSs), readily obtained from chitin, to give per-N-trifluoroacetyl derivatives offers an attractive route to size-defined COSs and derived glycoconjugates. It involves the use of various acceptor building blocks and trifluoromethyl oxazoline dimer donors prepared with efficiency and highly reactive in 1,2-trans glycosylation reactions. This method was applied to the preparation of the important symbiotic glycolipids which are highly active on plants and to the TMG-chitotriomycin, a potent and specific inhibitor of insect, fungal, and bacterial N-acetylglucosaminidases.


Assuntos
Quitina/química , Lipopolissacarídeos/química , Álcoois Açúcares/química , Biomassa , Glicosilação
13.
Plant Physiol ; 159(4): 1524-44, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22723084

RESUMO

Initially known for their role in the rhizosphere in stimulating the seed germination of parasitic weeds such as the Striga and Orobanche species, and later as host recognition signals for arbuscular mycorrhizal fungi, strigolactones (SLs) were recently rediscovered as a new class of plant hormones involved in the control of shoot branching in plants. Herein, we report the synthesis of new SL analogs and, to our knowledge, the first study of SL structure-activity relationships for their hormonal activity in garden pea (Pisum sativum). Comparisons with their action for the germination of broomrape (Phelipanche ramosa) are also presented. The pea rms1 SL-deficient mutant was used in a SL bioassay based on axillary bud length after direct SL application on the bud. This assay was compared with an assay where SLs were fed via the roots using hydroponics and with a molecular assay in which transcript levels of BRANCHED1, the pea homolog of the maize TEOSINTE BRANCHED1 gene were quantified in axillary buds only 6 h after application of SLs. We have demonstrated that the presence of a Michael acceptor and a methylbutenolide or dimethylbutenolide motif in the same molecule is essential. It was established that the more active analog 23 with a dimethylbutenolide as the D-ring could be used to control the plant architecture without strongly favoring the germination of P. ramosa seeds. Bold numerals refer to numbers of compounds.


Assuntos
Lactonas/química , Lactonas/farmacologia , Morfogênese/efeitos dos fármacos , Pisum sativum/efeitos dos fármacos , Pisum sativum/crescimento & desenvolvimento , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/crescimento & desenvolvimento , Bioensaio , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Hidroponia , Lactonas/síntese química , Modelos Biológicos , Oxirredução/efeitos dos fármacos , Pisum sativum/genética , Pisum sativum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Brotos de Planta/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade
14.
Chemistry ; 19(15): 4849-57, 2013 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-23420702

RESUMO

A new general access to A-ring aromatic strigolactones, a new class of plant hormones, has been developed. The key transformations include in sequence ring-closing metathesis, enzymatic kinetic resolution and a radical cyclization with atom transfer to install the tricyclic ABC-ring system. The activity as plant hormones for the inhibition of shoot branching in pea of various analogues synthesized by this strategy is reported.


Assuntos
Lactonas/síntese química , Pisum sativum/química , Reguladores de Crescimento de Plantas/síntese química , Lactonas/química , Lactonas/metabolismo , Estrutura Molecular , Pisum sativum/metabolismo , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/metabolismo , Relação Estrutura-Atividade
15.
J Org Chem ; 78(15): 7648-57, 2013 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-23845048

RESUMO

Tetra-O-acylated sulfolipids are metabolites found in the cell wall of Mycobacterium tuberculosis, the causative agent of tuberculosis. Their role in pathogenesis remains, however, undefined. Here we describe a novel access to model tetra-O-acylated trehalose sulfate derivatives having simple acyl chains. The trehalose core was regioselectively protected using a tandem procedure with catalytic iron(III) chloride hexahydrate and further desymmetrized. Model chiral fatty acids, prepared by a zinc-mediated cross-coupling, were incorporated into the trehalose core. The enantiomeric excess of the chiral fatty acids has been measured by natural abundance deuterium (NAD) 2D-NMR spectroscopy in a polypeptide based chiral liquid crystal. The synthetic approach established for the model compounds can easily be developed for the preparation of other analogues and natural sulfolipids.


Assuntos
Deutério/química , Lipídeos/síntese química , Mycobacterium tuberculosis/química , Anisotropia , Lipídeos/química , Espectroscopia de Ressonância Magnética , Conformação Molecular
16.
Glycobiology ; 21(6): 824-33, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21415035

RESUMO

Nod factors are lipochitoligosaccharides originally produced by the soil bacteria Rhizobia that are involved in the symbiotic process with leguminous plants. Some synthetic analogs of the Nod factors present a strong biological activity, and the conformational behavior of these molecules is of interest for structure/function studies. Nod factor analogs containing an insertion of a phenyl group in the acyl chain at the oligosaccharidic non-reducing end were previously synthesized (Grenouillat N, Vauzeilles B, Bono J-J, Samain E, Beau J-M. 2004. Simple synthesis of nodulation-factor analogues exhibiting high affinity towards a specific binding protein. Angew Chem Int Ed Engl. 43:4644). Conformational studies of natural compounds and synthetic analogs have been performed combining molecular dynamics simulations in explicit water and NMR. Data revealed that the glycosidic head group can adopt only restricted conformations, whereas chemical modifications of the lipid chains, highly flexible in a water environment, influence the global shape of the molecules. Collected structural data could be used in the future to rationalize and understand their biological activity and affinity toward a putative receptor.


Assuntos
Lipopolissacarídeos/química , Nodulação , Configuração de Carboidratos , Lipopolissacarídeos/metabolismo , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Simulação de Dinâmica Molecular , Nodulação/fisiologia , Rizosfera
17.
Chimia (Aarau) ; 65(1-2): 45-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21469444

RESUMO

Lipo-chitooligosaccharidic nodulation (Nod) factors produced by rhizobia are a class of signalling molecules that induce a symbiotic association between legumes and soil bacteria rhizobia leading to the formation of the nitrogen-fixing root nodule. They consist of a chitin oligomeric backbone N-acylated at the non-reducing unit and are equipped with a variety of substituents at both ends of the oligosaccharide. This brief account focuses on the different approaches developed for their synthesis with particular emphasis on glycosylation methods. Current use of these Nod factors or analogs as additives in agricultural applications has shown to be very promising for sustainable agriculture.


Assuntos
Agricultura , Lipopolissacarídeos/síntese química , Sequência de Carboidratos , Lipopolissacarídeos/química , Dados de Sequência Molecular , Fixação de Nitrogênio
18.
J Org Chem ; 75(5): 1783-6, 2010 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-20136154

RESUMO

The oxidative cleavage of 4,6-O-benzylidene acetals of glycopyranosides using dimethyldioxirane (DMDO) leads to the corresponding hydroxy-benzoates in excellent yields. With a proper choice of the neighboring protecting groups, this oxidative fragmentation provides the 6- or 4-hydroxyl derivatives in a highly regioselective manner.

19.
Chemistry ; 15(21): 5195-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19353608

RESUMO

A regio- and stereocontrolled solution for a selective modification at the C-2 or C-4 position of N-acetylneuraminic acid involves the use of allylic substitution catalyzed by palladium. As illustrated in the scheme, regioselective malonylation is under the strict influence of the ligands associated with the allylpalladium complex.


Assuntos
Carboidratos/química , Ácido N-Acetilneuramínico/química , Paládio/química , Compostos Alílicos , Catálise , Ligantes , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade
20.
Chem Commun (Camb) ; 55(87): 13074-13077, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31588930

RESUMO

In this study, we report the first synthesis of an alkyne-based trehalose monomycolate probe containing a ß-hydroxylated fatty acid and an α-branched chain similar to those of the natural mycolic acid. We demonstrate its utility for the labeling of the mycomembrane of Corynebacteria as well as for the study of mycoloyltransferases.


Assuntos
Aciltransferases/análise , Membrana Celular/química , Corynebacterium/enzimologia , Corantes Fluorescentes/química , Ácidos Micólicos/química , Aciltransferases/metabolismo , Membrana Celular/metabolismo , Corynebacterium/citologia , Corantes Fluorescentes/síntese química , Estrutura Molecular , Ácidos Micólicos/síntese química
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