Steroid substrate-induced epimerase mechanism in the active site of the human 11β-hydroxysteroid dehydrogenase type 1

Cytochrome P4507B1 7[alpha]-hydroxylates dehydroepiandrosterone (DHEA), epiandrosterone (EpiA) and 5[alpha]-androstane-3[beta],17[beta]-diol (Adiol). 11[beta]-Hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1) interconverts 7[alpha]- and 7[beta]- forms. Whether the inter-conversion proceeds through oxido-reductive steps or epimerase activity is investigated. Experiments using ^3^H-labeled 7[beta]-hydroxy-DHEA, 7[beta]-hydroxy-EpiA and 7[beta]-hydroxy-Adiol show the ^3^H-label to accumulate in 7-oxo-DHEA trap but neither in 7-oxo-EpiA nor 7-oxo-Adiol traps. Computed models of 7-oxygenated steroids dock in the active site of 11[beta]-HSD1 either in a flipped or turned form relative to cortisone and cortisol. 7-Oxo-steroid reduction in 7[alpha]- or 7[beta]-hydroxylated derivatives results from either turned or flipped forms. 11[beta]-HSD1 incubation in H~2~^18^O medium with each 7-hydroxysteroid did not incorporate ^18^O in 7-hydroxylated derivatives of EpiA and Adiol independently of the cofactor used. Thus oxido-reductive steps apply for the interconversion of 7[alpha]- and 7[beta]-hydroxy-DHEA through 7-oxo-DHEA. Epimerisation may proceed on the 7-hydroxylated derivatives of EpiA and Adiol through a mechanism involving the cofactor and Ser170

Study on the Cloud Point Extraction of Gd(III) with 8-Hydroxyquinoline

International audienc

Oxydation catalytique d’aldéhyde en flux continu et sous ultrasons

National audienc

Improved Reactor Productivity for the Safe Photo-Oxidation of Citronellol Under Visible Light LED Irradiation

International audienc

Metal-free, visible light-promoted aerobic aldehydes oxidation

International audienc

Unusual reactivities of acridine derivatives in catalytic hydrogenation. A combined experimental and theoretical study

International audienceHydrogenation of acridine derivatives over Rh/Al2O3, has been studied. Strong influence of the pyrrolidino-substituent on the reduction pathway and reductions products was found. When, the reaction was performed on the unsubstituted acridine nucleus full conversion was obtained in 8 h. Under the same conditions, when a pyrrolidine substituent was settled on the central ring of acridine (9-position), a pure product was obtained with the two lateral carbocycles reduced whereas the central heterocyclic ring was not reduced. When the pyrrolidin e substituent was at the 1-position, pure partially reduced central heterocyclic ring was obtained, but the compound was rapidly re-oxidized by air. In order to clarify such substituent effect, theoretical calculations were performed. Considering the energies and thermodynamic values of each intermediate and product as well as the interaction with the catalyst surface, the selectivity and diversity in the reduced product formation were partially explained and different reaction pathways were drawn according to the substitution pattern on the acridine scaffold

A mild titanium-based system for the reduction of amides to aldehydes

International audienceA mild method for the reduction of amides to aldehydes using 1,1,3,3-tetramethyldisiloxane/titanium(IV) isopropoxide reducing system is described. The reaction occurs under mild conditions and allows the reduction of aromatic as well as aliphatic, tertiary amides to the corresponding aldehydes, in good yields. This methodology was extended to the reduction of aromatic secondary and primary amides to the corresponding aldehydes

An improved and safer synthesis of (R)- and (S)-4,4'-diaminomethyl-BINAP.

International audience(R)- and (S)-4,4′-diaminomethyl-BINAP were prepared in three steps from enantiomerically pure BINAPO in a global yield of 52 %. A regioselective bromination of BINAPO with NBS in HMimPF6 gave the desired 4,4′-dibromo-BINAPO in quantitative yield, and the recyclability of the ionic liquid was demonstrated. Copper cyanide cyanation of 4,4′-dibromo-BINAPO gave the 4,4′-dicyano-BINAPO in 70 % yield. Both enantiomers were characterized by NMR spectroscopy and HPLC analysis, and the structures were confirmed by X-ray crystallography. The cyano and phosphane oxide groups of the resulting 4,4′-dicyano-BINAPO were reduced in one step to the corresponding 4,4′-diaminomethyl-BINAP by using tetramethyldisiloxane/Ti(OiPr)4 in 75 % yield