Charles Gauthier

Charles Gauthier
Institut National de la Recherche Scientifique | INRS · Institute Armand-Frappier Research Centre

PhD in Organic Chemistry

About

60
Publications
10,570
Reads
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1,273
Citations
Additional affiliations
June 2020 - present
Institut National de la Recherche Scientifique
Position
  • Professor (Associate)
June 2016 - June 2020
Institut National de la Recherche Scientifique
Position
  • Professor (Assistant)
May 2012 - present
University of Québec in Chicoutimi
Position
  • Professor (Associate)
Description
  • Isolation of bioactive natural products. Synthesis of lupane-type triterpenoid derivatives. Development of novel plant-derived vaccine adjuvants.

Publications

Publications (60)
Article
Burkholderia pseudomallei and Burkholderia mallei are potential bioterrorism agents. They express the same capsular polysaccharide (CPS), a homopolymer featuring an unusual [→3)-2-O-acetyl-6-deoxy-β-d-manno-heptopyranosyl-(1→] as the repeating unit. This CPS is known to be one of the main targets of the adaptive immune response in humans and theref...
Article
Full-text available
The synthesis of the repeating unit of the immunogenic beta-Kdo-containing exopolysaccharide produced by Burkholderia pseudomallei and bacteria of the B. cepacia complex is described. The target tetrasaccharide was synthesized via stereoselective 1,2-cis- and 1,2-trans-galactosylations and beta-Kdosylation. A [3 + 1] coupling reaction between a tri...
Article
Full-text available
3-Deoxy-beta-d-manno-oct-2-ulosonic acid (beta-Kdo) glycosides are mainly found in capsular polysaccharides (CPS) and extracellular exopolysaccharides (EPS) from Gram-negative bacteria. These compounds have profound biological implications in immune response and act as virulence factors. We have developed a novel methodology for the stereoselective...
Article
Full-text available
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. Studies have highlighted the importance of Bp and Bm lipopolysaccharides (LPS) as vaccine candidates. Here we describe the synthesis of seven oligosaccharides as the minimal st...
Article
Full-text available
3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) bio-synthetic pathway is a promising target in antibacterial drug discovery. Herein, we report the total synthesis of 6-amino-2,6-dideoxy-α-Kdo in 15 steps from D-mannose as a potential inhibitor of Kdo-processing enzymes. Key steps of the synthetic sequence involve a Horner−Wadsworth−Emmons reaction for th...
Article
Full-text available
Plant innate immunity is activated upon perception of invasion pattern molecules by plant cell-surface immune receptors. Several bacteria of the genera Pseudomonas and Burkholderia produce rhamnolipids (RLs) from l -rhamnose and ( R )-3-hydroxyalkanoate precursors (HAAs). RL and HAA secretion is required to modulate bacterial surface motility, biof...
Article
Burkholderia gladioli is a Gram-negative bacterium that biosynthesizes a cocktail of potent antimicrobial compounds, including the antifungal phenolic glycoside sinapigladioside. Herein, we report the total synthesis of the proposed structures of gladiosides I and II, two structurally related phenolic glycosides previously isolated from B. gladioli...
Preprint
Rhamnolipids are a specific class of microbial surfactants, which hold great biotechnological and therapeutic potential. However, their exploitation at the industrial level is hampered because they are mainly produced by the opportunistic pathogen Pseudomonas aeruginosa . The non-human pathogenic bacterium Pantoea ananatis is an alternative produce...
Article
Carbohydrates and their conjugates are not only involved in important biological processes but are also regarded as promising therapeutics and prophylactics. Over the last century, several glycosylation methodologies, glycosyl donors, and protecting groups have been developed and some of them have found broad synthetic applications in carbohydrate...
Preprint
Full-text available
Plant innate immunity is activated upon perception of invasion pattern molecules by plant cell-surface immune receptors. Several bacteria of the genera Pseudomonas and Burkholderia produce rhamnolipids (RLs) from L- rhamnose and ( R )-3-hydroxyalkanoate precursors (HAAs). RL and HAA secretion is required to modulate bacterial surface motility, biof...
Article
The soil bacterium Burkholderia thailandensis produces 2-alkyl-4(1 H )-quinolones that are mostly methylated 4-hydroxyalkenylquinolines, a family of relatively unstudied metabolites similar to molecules also synthesized by Pseudomonas aeruginosa . Several of the methylated 4-hydroxyalkenylquinolines have antimicrobial activity against other species...
Article
The Burkholderia genus offers a promising potential in medicine because of the diversity of biologically active natural products encoded in its genome. Some pathogenic Burkholderia spp. biosynthesize a specific class of antimicrobial 2-alkyl-4(1H)-quinolones, i.e., 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and their N-oxide derivatives (HMAQNO...
Article
As one of the main causes of bacterial diarrhea and a major risk factor for triggering Guillain-Barré autoimmune syndrome, campylobacteriosis, i.e., Campylobacter spp. infections, represents a major health issue worldwide. There is thus a pressing need for developing an effective and broad-coverage campylobacteriosis vaccine. Campylobacter jejuni,...
Preprint
The bacterium Burkholderia thailandensis produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology of this soil-dwelling bacterium. In liquid co-culture experiments, B. thailandensis secretes an antimicrobial that nearly eliminates another soil bacterium, Bacillus subtilis . To identify the antimicrobial, we...
Article
Full-text available
The development of multicellularity is a key evolutionary transition allowing for differentiation of physiological functions across a cell population that confers survival benefits; among unicellular bacteria, this can lead to complex developmental behaviors and the formation of higher-order community structures. Herein, we demonstrate that in the...
Preprint
Full-text available
The Burkholderia genus offers a promising potential in medicine because of the diversity of biologically active natural products encoded in its genome. Some pathogenic Burkholderia spp. biosynthesize a specific class of antimicrobial 2-alkyl-4(1H)-quinolones, i.e., 4-hydroxy-3-methyl-2-alkenylquinolones (HMAQs) and their N-oxide derivatives (HMAQNO...
Chapter
Bioterrorism is seen as a serious threat in today’s world. Some bacterial pathogens have been listed as potential bioterrorism agents due to their low infectious doses, ability to be aerosolized, high transmission rate, and tolerance to a wide range of environmental conditions. This list includes the CDC Tier 1 Select Agents Bacillus anthracis, Yer...
Chapter
The re-emergence of pathogenic bacteria and their growing resistance to currently used antibiotics has prompted the search for new therapeutic targets and antibiotics. As a highly conserved and essential element of Gram-negative bacteria lipopolysaccharides (LPS), 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) biosynthesis is an exquisite target for the...
Article
Full-text available
Betulinic acid and ursolic acid are ubiquitous, naturally-occurring triterpenoids exhibiting various pharmacological activities including cytotoxic and anti-inflammatory activities. However, these triterpenoids display unfavorable pharmacokinetic properties as well as low aqueous solubility. It has been shown that the presence of α-L-rhamnose moiet...
Article
Melioidosis and glanders, respectively caused by the Gram-negative bacteria Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), are considered as urgent public health issues in developing countries and potential bioterrorism agents. Bp and Bm lipopolysaccharides (LPS) have been identified as attractive vaccine candidates for the developmen...
Article
A seven-step total synthesis of the original scaffold of cytotoxic dirchromones involving an unprecedented soft-enolization Baker-Venkataraman rearrangement was designed. The methodology enabled access to naturally occurring dirchromone 1 (21% overall yield) at gram-scale, which was screened for cytotoxicity against 13 cancer cell lines. The scope...
Article
The bacterium Pantoea ananatis was reported to produce glycolipid biosurfactants of unknown structures. Herein, we present the isolation and structural determination of ananatoside A, the main congener of a new family of 15-membered macrodilactone-containing glucolipids. The structure of ananatoside A was elucidated via chemical degradation and spe...
Article
Covering: up to 2018 Burkholderia species are a vast group of human pathogenic, phytopathogenic, and plant- or environment-associated bacteria. B. pseudomallei, B. mallei, and B. cepacia complex are the causative agents of melioidosis, glanders, and cystic fibrosis-related infections, respectively, which are fatal diseases in humans and animals. Du...
Article
Full-text available
Betulin has a wide range of biological and pharmacological properties with its anticancer activity attracting most of the attention as it offers a possible alternative treatment to chemotherapy. However, betulin’s in vivo biological effectiveness is limited by its poor solubility. As such, we synthesized polar glycosylated derivatives to increase i...
Article
Full-text available
Background Many plants of boreal forest of Quebec have been used by Native Americans to treat a variety of microbial infections. However, the antiviral activities of these plants have been seldom evaluated on cellular models to validate their in vitro efficiencies. In this study, Cornus canadensis L. (Cornaceae), a plant used in Native American tra...
Article
There is nowadays an urgent need for developing novel generations of antibiotic agents due to the increased resistance of pathogenic bacteria. As a rich reservoir of structurally diverse compounds, plant species hold promise in this regard. Within this framework, we isolated a unique series of antibacterial flavonoids, named balsacones N-U, featuri...
Article
Eight non-carotenoid tetraterpenoids, abibalsamins C-J (3-10), were isolated from the oleoresin of Abies balsamea. Their chemical structures were determined based on analysis of 1D/2D NMR and MS data. The assignment of their relative configurations was accomplished using homonuclear coupling constants in tandem with ROESY data. However, the presenc...
Article
Burkholderia pseudomallei is the bacterium responsible for melioidosis, an infectious disease with high mortality rates. Since melioidosis is a significant public health concern in endemic regions and the organism is currently classified as a potential biothreat agent, the development of effective vaccines and rapid diagnostics is a priority. The c...
Article
A phytochemical investigation of buds from the hardwood tree Populus balsamifera led to the isolation of six new cinnamoylated dihydrochalcones as pairs of racemates and one as a racemic mixture along with the known compound iryantherin-D (2), the absolute configuration of which was determined for the first time. The structures of balsacones J (1),...
Article
The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these a-d-GlcNAc and a-d-GalNAc mimics utilizes a beta-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring a-HGJ and a-HNJ. The a-d-GlcNAc-configured imino...
Article
The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these α-d-GlcNAc and α-d-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring α-HGJ and α-HNJ. The α-d-GlcNAc-configured iminosug...
Article
The first synthesis of 1,2-trans-homoiminosugars devised as mimics of β-d-GlcNAc and α-d-ManNAc is described. Key steps include a regioselective azidolysis of a cyclic sulfite and a β-amino alcohol skeletal rearrangement applied to a polyhydroxylated azepane. The β-d-GlcNAc derivative has been coupled to serine to deliver an iminosugar C-amino acid...
Article
Hellecaucaside A, a new disaccharide nucleoside featuring a 2'-O-alpha-D-ribofuranosyluridine skeleton and a 4-hydroxybenzoyl group at the 50 position, was isolated from the underground part of Helleborus caucasicus. The structure of the compound was elucidated by means of chemical degradation and spectroscopic analyses, such as 1D/2D NMR, chiral-G...
Article
X-ray crystallography and kinetic isotopic effects applied to glycosyl-processing enzymes in complex with their substrates or inhibitors allowed deciphering of the sugar ring conformation at the atomic level. This information, crucial for the development of potent and selective inhibitors of these enzymes, has been extensively exploited to design c...
Article
Full-text available
Synthetic functional mimics of the O-antigen from Shigella flexneri 2a are seen as promising vaccine components against endemic shigellosis. Herein, the influence of the polysaccharide non-stoichiometric di-O-acetylation on antigenicity is addressed for the first time. Three decasaccharides, representing relevant internal mono- and di-O-acetylation...
Article
Full-text available
Phytochemical analysis of A. balsamea oleoresin led to the isolation of three new 3,4-seco-lanostane triterpenoids 1-3, one new cycloartane triterpenoid 4 along with fourteen known terpenoids. Structure determinations were based on extensive 1D/2D NMR, IR and MS spectroscopic analyses, and comparison with literature data. The isolated compounds wer...
Article
Extensive analysis by NMR spectroscopy of the delipidated lipopolysaccharide of Shigella flexneri serotype 6 strain MDC 2924-71 confirmed the most recently reported structure of the O-antigen repeating unit as {→4)-β-D-GalpA-(1→3)-β-D-GalpNAc-(1→2)-α-L-Rhap3Ac/4Ac-(1→2)-α-L-Rhap-(1→}, and revealed the non-stoichiometric acetylation at O-3C/4C. Inpu...
Article
A new series of betulinic acid and betulin derivatives were synthesized by introducing a D-glycerol moiety at the C-3 and/or C-28 positions of the lupane skeleton. The resulting glyceryl esters were evaluated in vitro for their cytotoxic activity against A549, DLD-1 and WS1 human cell lines. The structure-activity relationships study revealed that...
Article
Full-text available
Abibalsamins A (1) and B (2), two unprecedented tetraterpenoids featuring a 3,4-seco-rearranged lanostane system fused with a β-myrcene lateral chain via a [4 + 2] Diels-Alder cycloaddition, were isolated from the oleoresin of Abies balsamea. Their structures were elucidated by means of extensive 2D NMR, IR, and MS spectroscopy analyses. The absolu...
Article
Full-text available
Lupeol, betulin and betulinic acid are members of the so-called lupane-type triterpenoids. These natural products found worldwide in quite of lot of vegetables, fruits and plant species exhibit promising pharmacological activities including anti-inflammatory, anti-HIV and antitumor activities. Nevertheless, the poor pharmacokinetic properties of th...
Article
22(17->28)abeo-Lupene derivatives 5a and 6a were obtained after the acid-catalyzed E-ring expansion of 3-acetylbetulin (1a). Glycosylation of these dehydrated triterpenoids using Schmidt’s trichloroacetimidate sugar donors in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) provided the new anhydrobetulin saponins 7b–7e in which th...
Article
Full-text available
This short review describes the recently reported semi- and total syntheses of naturally occurring triterpenoid saponins. Accent is placed on natural monodesmosidic and bidesmosidic saponins of the oleanane- and lupane-type that possess potent pharmacological properties including cytotoxic and antitumor activities.
Article
The concise synthesis, via a stepwise glycosylation approach, of lupeol, betulin and betulinic acid O-glycosides bearing a chacotriosyl moiety at the C-3 position is described. All neosaponins as well as their rearrangement products of the germanicane-type were evaluated in vitro for their anticancer and haemolytic activities. Although betulinic ac...
Article
The synthesis of 28-O-b-D-glucuronide betulinic acid, an acyl glucuronide derivative, was successfully carried out for the first time using commercially available peracetylated methyl glucuronate bromide under phase-transfer conditions. The target compound could be used in an anticancer prodrug monotherapy (PMT)strategy since it is non-cytotoxic, n...
Article
alpha-Bisabolol beta-d-fucopyranoside, a cytotoxic naturally occurring compound, was efficiently synthesized along with five other alpha-bisabolol glycosides (beta-d-glucoside, beta-d-galactoside, alpha-d-mannoside, beta-d-xyloside and alpha-l-rhamnoside). Glycosidation of alpha-bisabolol was performed using Schmidt's inverse procedure and provided...
Article
The haemolysis of red blood cells inducing toxicity in most animals including humans is a major drawback for the clinical development of saponins as antitumour agents. In this study, the haemolytic and cytotoxic activities as well as the membrane cell permeabilization property of a library of 31 semi-synthetic and natural lupane- and oleanane-type...
Article
The naturally occurring cytotoxic saponin 28-O-beta-d-glucopyranosylbetulinic acid 3beta-O-alpha-l-arabinopyranoside (3) was easily synthesized along with seven bidesmosidic saponins starting from the lupane-type triterpenoids betulin (1) and betulinic acid (2). As highlighted by the preliminary cytotoxicity evaluation against A549, DLD-1, MCF7, an...
Article
A concise synthesis of naturally occurring betulinic acid saponins bearing an a-L-rhamnopyranosyl-(1->2)-a-L-arabinopyranoside moiety at the C-3 position is described. Betulinic acid 3b-O-a-L-rhamnopyranosyl-(1->2)-[b-D-glucopyranosyl-(1->4)]-a-L-arabinopyranoside isolated from Pulsatilla koreana and 28-O-b-D-glucopyranosyl betulinic acid 3b-O-a-L-...
Article
Full-text available
Phytochemical investigations of the MeOH extract of Betula papyrifera inner bark led to the isolation of ten phenolic compounds of the following types: diarylheptanoid glycosides (1-4), a diarylheptanoid (5), a lignan (6), flavonoids (7-8) and chavicol glycosides (9-10). Among them, the diarylheptanoid glycoside, (S)-1,7-bis-(4-hydroxyphenyl)-hepta...
Article
Germanicane-type triterpenes allobetulin (3) and 28-oxoallobetulin (4) can be obtained by the Wagner-Meerwein rearrangement of the more available lupane-type triterpenes betulin (1) and betulinic acid (2), respectively. The medical uses of betulinic acid (2) and its derivatives are limited because of their poor hydrosolubility and pharmacokinetics...
Article
The weak hydrosolubility of betulinic acid (3) hampers the clinical development of this natural anticancer agent. In order to circumvent this problem and to enhance the pharmacological properties of betulinic acid (3) and the lupane-type triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta-D-glucosides, alpha-L-rhamnosid...
Article
The weak hydrosolubility of betulinic acid (3) hampers the clinical development of this natural anticancer agent. In order to circumvent this problem and to enhance the pharmacological properties of betulinic acid (3) and the lupane-type triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta-D-glucosides, alpha-L-rhamnosid...

Questions

Questions (2)
Question
We are looking to order lithium azide (~5 g, solid form) but are unable to find any companies who sell it. Sigma-Aldrich and other companies sell 20% LiN3 in H2O, however we do need it as a solid. Obviously, we are aware that this compound is potentially explosive at high temperatures.  Does anyone know where I could get some?
Question
I have an oligosaccharide bearing an acetyl group on a secondary hydroxyl that I suspect sensible to the freeze-drying process. I was wondering if anyone has already had this behavior on a similar compound or if someone has already observed the degradation of any compound/functionality using freeze-drying (lyophilization)?

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Projects (2)
Archived project
I would like to determinate (1) the regulation of the hmqABCDEFG operon (2) its interaction with the main QS and (3) the role of HMAQs - produced by the system - in Burkholderia cepacia complex.