Juba Ghouilem

Description principale de l'offre d'emploi :
Le sujet porte sur le développement de nouvelles méthodologies en synthèse organique. Le candidat sélectionné sera impliqué dans le développement de ces nouvelles méthodologies, de l'optimisation, le champ d'application à la synthèse de petits fragments de produits naturels.
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Tetrodotoxin and congeners are specific voltage-gated sodium channel blockers that exhibit remarkable anesthetic and an-algesic effects. Here, we present a scalable asymmetric synthesis of TTX and 9-epiTTX from the abundant chemical feed-stock furfuryl alcohol. The optically pure cyclohexane skeleton was assembled via a stereoselective Diels-Alder reaction. The dense heteroatom substituents were established sequentially by a series of functional group interconversions on highly oxygenated cyclohexane frameworks, including a chemoselective cyclic anhydride opening, and a decarboxylative hydrox-ylation. An innovative SmI2-mediated concurrent fragmentation, an oxo-bridge ring opening and ester reduction followed by an Upjohn dihydroxylation delivered the highly oxidized skeleton. Ruthenium-catalyzed oxidative alkyne cleavage and formation of the hemiaminal and orthoester under acidic conditions enabled the rapid assembly of TTX, anhydro-TTX, 9-epiTTX, and 9-epi lactone-TTX.

Description principale de l'offre d'emploi :
- Recherche bibliographique
- Synthèse organique
- Caractérisation de molécules organiques (RMN, HPLC, spectrométrie de masse)
- Validation de résultats
- Rédaction de rapport
- Présentation orale des résultats et interaction avec le consortium de recherche
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Direct C-H bond functionalization is a useful strategy for the straightforward formation of C-C and C-Heteroatom bonds. In the present work, a unique approach for the challenging electrophilic Au-catalyzed alpha-C-H bond functionalization of tertiary amines is presented. Electronic, steric and conformational synergistic effects exerted by the use of a malonate unit in the substrate were key to the success of this transformation. This new reactivity was applied to the synthesis of tetrahydro-g-carboline products which, under oxidative conditions, could be converted into valuable structural motifs found in bioactive alkaloid natural products

Synthesis
DOI: 10.1055/a-1823-3604

Synthesis of sulfonyl halides using sodium hypochlorite pentahydrate (NaOCl·5H2O) crystals was studied in detail, considering the reaction rate and yield of the desired product. NaOCl·5H2O reacted with disulfides or thiols in acetic acid to produce sulfonyl chlorides. The yields of the desired sulfonyl chlorides were enhanced when the reaction was performed in (trifluoromethyl)benzene under a CO2 atmosphere. The generation of hypochlorous acid (HOCl) was essential for both reactions. Similarly, sulfonyl bromides were prepared via the reaction of disulfides or thiols with sodium bromide and NaOCl·5H2O crystals in acetic acid owing to the generation of hypobromous acid (HOBr). However, the reaction could not proceed in (trifluoromethyl)benzene under a CO2 atmosphere because bromine was produced instead of HOBr.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

The introduction of remote stereochemistry via successive Type I Anion Relay Chemistry (ARC) coupling of commercially available enantioenriched epoxides has enabled a 20-step total synthesis of (−)-bastimolide A. The streamlined assembly and manipulation of ARC products demonstrates a versatile approach that could be leveraged toward other polyhydroxylated macrolides

Abstract

A highly convergent total synthesis of (−)-bastimolide A (1), a polyhydroxy antimalarial macrolide, has been achieved via a longest linear sequence of twenty steps from commercially available glycidyl ethers. Type I Anion Relay Chemistry (ARC) coupling tactics enable rapid construction of the molecule's 1,5-polylol backbone. A late-stage B-alkyl Suzuki–Miyaura union and an Evans-modified Mukaiyama macrolactonization generate the forty-membered Z-α,β-unsaturated macrocyclic lactone.

Integrative self-assembly of Pd^II cations with an enantiopure helicene-based ligand and non-chiral but emissive fluorenone ligands yields a series of Pd₂L₂L′₂ heteroleptic coordination cages, showing circularly polarized luminescence (CPL) from the non-chiral moiety. Modulation of the chiroptical properties is achieved by ligand modification or guest binding, achieving an up to 4-fold enhancement of CPL intensity.

Abstract

Multicomponent metallo-supramolecular assembly allows the rational combination of different building blocks. Discrete multifunctional hosts with an accessible cavity can be prepared in a non-statistical fashion. We employ our shape-complementary assembly (SCA) method to achieve for the first time integrative self-sorting of heteroleptic Pd^II cages showing guest-tunable circularly polarized luminescence (CPL). An enantiopure helicene-based ligand (M or P configuration) is coupled with a non-chiral emissive fluorenone-based ligand (A or B) to form a series of Pd₂L₂L′₂ assemblies. The modular strategy allows to impart the chiral information of the helicenes to the overall supramolecular system, resulting in CPL from the non-chiral component. Guest binding results in a 4-fold increase of CPL intensity. The principle offers potential to generate libraries of multifunctional materials with applications in molecular recognition, enantioselective photo-redox catalysis and information processing.

The importance of O/N-glycosides as biologically active compounds cannot be overstated. This study is focused on the functionalization of glycals and ribals at the C2 position with alkyl, vinyl, aryl, heteroaryl and strained ring substituents. The functionalized glycals and ribals were transformed into 2-C-deoxyglycosides and 2’-C-deoxynucleosides. The application to the synthesis of an analogue of cladribine and clofarabine is described.

Abstract

The synthesis of 2-C-glycals and 2-C-ribals was achieved in good yields using a nickel-catalyzed cross-coupling between 2-iodoglycals and 2-iodoribal respectively and Grignard reagents. The prepared 2-C-glycals and ribals were then transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides and 2’-C-2’-deoxynucleosides. The developed method was applied to the synthesis of a 2-chloroadenine

2’-deoxyribonucleoside – a structural analogue of cladribine (Mavenclad®, Leustatin®) and clofarabine (Clolar®, Evoltra®), two compounds used in the treatment of relapsing-remitting multiple sclerosis and hairy cell leukemia.

We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is uniquely enabled by the combination of PdI2 as the precatalyst and HFIP solvent. Structurally complex nitroalkane products, including nitro-containing carbo- and heterocycles, are prepared under operationally convenient conditions without the need for toxic or corrosive reagents. Deuterium labeling experiments and isolation of a catalytically relevant intermediate shed light on the reaction mechanism. By taking advantage of different catalytic activation modes, we demonstrate orthogonal methods for site-selective functionalization of a polyfunctional nitroalkyl ketone.

Chemistry Letters, Volume 51, Issue 2, Page 94-98, February 2022.

Spectroscopy deciphers censored passages in 200-year-old letters between last French queen and the man rumoured to be her lover