Catherine Mirand

Inhibition of Gelatinase A by Oleic Acid

Oleic acid ( cis -9-octadecenoic acid, OA) inhibited the formation of lung metastases from subcutaneous implantation of colon carcinoma cells in mice, such an inhibition being associated with a decrease of gelatinase A (MMP-2) activity in tumor-tissue extracts. 1 We similarly showed that OA considerably reduced MMP-2 activity released into the culture medium conditioned by oncogene-transformed human bronchial epithelial cells (BZR cells). 2 The interaction between this fatty acid and MMP-2 was further analyzed. We first confirmed the inhibitory capacity of OA towards MMP-2 activity using a fluorogenic quenching substrate, (7-methoxycoumarin-4-yl)acetylL -Pro-Leu-GlyLeu-[N-3-(2,4-dinitrophenyl)L -2,3-diaminopropionyl]-Ala-Arg-NH 2 (Mca-Pro-LeuGly-Leu-Dpa-Ala-Arg-NH 2 ). 2

Further alkaloids from strychnos longicaudata and strychnos ngouniensis

Abstract Twenty four alkaloids have been isolated and identified from the root and stem barks of Strychnos longicaudata Gilg and Strychnos ngouniensis Pellegrin. Among these, 17 alkaloids are isolated for the first time; the novel bisindole series represented by longicaudatine includes now two other compounds: longicaudatines F and Y; besides ngouniensine, its epimer epingouniensine has been isolated along with two glucosyl-ngouniensines. Other new alkaloids include tubotaiwinal and several bases possessing the akuammicine skeleton.

MMPs inhibitors: new succinylhydroxamates with selective inhibition of MMP-2 over MMP-3.

Some ilomastat analogues featuring an isobutylidene group or a 2-substituted indole nucleus were synthesized to evaluate their inhibitory activities against gelatinase A and stromelysin-1. Potent MMP-2 inhibition and good selectivity for that enzyme have been observed for compounds 1a, 2 and 22.

Improved Enantioselective Synthesis of (−)-Linderol A: Hindered Rotation about Aryl−Csp3 Bond

An improved enantioselective total synthesis of (-)-linderol A has been achieved via a five-step reaction with a 21% overall yield, starting from phloroacetophenone and (-)-alpha-phellandrene, two commercially available reagents. In the diastereoselective epoxidation step, the analysis of the two endocyclic epoxide intermediates reveals a hindered sp(2)-sp(3) rotation, which results in rotational diastereoisomers.

The markovnikoff hydroboration of a trisubstituted olefin

Hydroboration-oxidation of akuammicine 1 mainly gave the tertiary alcohol 2 Hydroboration-oxidation of double bonds is a well known anti-Markovnikoff process1,2. In the course of applications of this method to the indole alkaloid field, the following Markovnikoff hydration of a trisubstituted olefin was surprisingly observed :

Atropisomerism about Aryl–C(sp3) Bonds: Conformational Behavior of Substituted Phenylcyclohexanes in Solution

A catalytic hydrogenation of cannabidiol derivatives known as phenylcyclohexenes was used to prepare epimeric (1R,1S) and/or rotameric (M,P) phenylcyclohexanes. The reaction is diastereoselective, in favor of the 1S epimer, when large groups are attached to the phenyl ring. For each epimer, variable-temperature NMR experiments, including EXSY spectroscopy and DFT calculations, were used to determine the activation energies of the conformational exchange arising from the restricted rotation about the aryl-C(sp(3)) bond that led to two unequally populated rotamers. The conformational preference arises essentially from steric interactions between substituents vicinal to the pivot bond. The conformers of epimers (1S)-2e,f show high rotational barriers of up to 92 kJ mol(-1), unlike those of (1R)-2e,f and with much lower barriers of ∼72 kJ mol(-1). The height of the barriers not only depends on the substituents at the axis of chirality but also is influenced by the position of a methyl group on the monoterpene ring. The feature most favorable to high rotational barriers is when the methyl at C1 lies equatorially. This additional substituent effect, highlighted for the first time, seems fundamental to allowing atropisomerism in hindered ortho-substituted phenylcyclohexanes.

N-Benzene-sulfonyl-indole as terminator in a biomimetic polyene cyclization: synthesis of a pentacyclic indolosesquiterpene

Abstract Epoxide 14 was cyclized with BF 3 to the pentacyclic derivative 17 , which was further elaborated to 19 , a stereoisomer of the natural indolosesquiterpene polyveoline.

Synthesis of 3-ω-epoxido farnesyl indoles, intermediates in the biogenesis of sesquiterpenic indole alkaloids

Abstract Epoxides 1a,b, the probable bioprecursors of a serie of indoloterpene alkaloids, were synthezised from indole and farnesyl bromides through application of the Van Tamelen regiospecific epoxidation process to the derived N-acylindolines 14a,b.