Low temperature syntheses of thioketals from enol ethers and carbonyl compounds

International audienc

Towards a [4+2] Route to (+/-)-decarestrictines J and H: Synthesis of a Bicyclic Key-intermediate

International audienceTowards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Towards a [4+2] Route to ()-decarestrictines J and Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud Martel [b], Duang Buddhasukh [a], Eric Brown [b], Sopa Chewchanwuttiwong [a], Arnaud We describe here the development of an approach to the synthesis of 3-oxo-7-hydroxy-9-decanolides of biological interest. This strategy involves two key steps : the inverse electron demand Hetero-Diels-Alder reaction of an original dienophile (1,5-dimethoxy-cyclohexa-1,4-diene), which will ensure the construction of an advanced structure in a very short number of steps, and the ring opening of a functionalized bicyclic lactol, leading to the requisite decanolide. The diastereocontrolled synthesis of such a lactol will be detailed in this communication

δ-Valerolactamic Quaternary Amino Acid Derivatives : Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties

International audienceEnantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetic

Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated Turn-Inducing Properties

International audienceEnantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce β-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetic

Phytochemical, anti-Acanthamoeba, and anti-adhesion properties of Garcinia mangostana flower as preventive contact lens solution

Acanthamoeba keratitis infection extends due to the growing number of contact lens users. Indigenous plants including Garcinia mangostana play a vital role in human health and well being. Many species of this plant have been reported with myriads of potent medicinal properties. However, the aims of this study were, for the first time, to isolate compounds from the flower of G. mangostana and to test their anti-Acanthamoeba and antiadhesion activity against Acanthamoeba triangularis. Powdered flowers of G. mangostana were extracted and chromatographed on a silica gel column. The structures of the compounds were established with the aid of 1 H NMR. More so, the anti-Acanthamoeba and anti-adhesion properties were tested on a 96-well polystyrene microtiter plate and soft contact lenses. Scanning electron microscope (SEM) was used to determine the features of A. triangularis on contact lenses. Eight pure compounds were obtained, namely 9-hydroxycalabaxanthone, tovophillin A, garcinone E, garcinone B, α-mangostin, gartinin, 8-deoxygartinin and γ-mangostin. The extract and pure compounds exhibited anti-Acanthamoeba activity with MIC values in the range of 0.25–1 mg/mL. In addition, the extract and α-mangostin displayed significant activity against the adhesion of A. triangularis trophozoites both in polystyrene plate and in contact lenses at 0.5 × MIC (0.25 mg/mL). Furthermore, α-mangostin has the potential to remove A. triangularis adhesion in contact lenses similar to a commercial multipurpose solution (MPS). SEM study confirmed that crude extract and α-mangostin are effective as solutions for contact lenses, which removed A. triangularis trophozoites within 24 h. Alpha-mangostin was non-toxic to Vero cells at a concentration below 39 μM in 24 h. Crude extract of G. mangostana flower and its α-mangostin serve as candidate compounds in the treatment of Acanthamoeba infection or as lens care solution, since they can be used as a source of natural products against Acanthamoeba and virulence factor associated with the adhesion of A. triangularis