Isabelle Ripoche

A new stereoselective synthesis of chiral optically pure 4-piperidones

Abstract A novel approach to optically pure and functionalized 4-piperidones using diene tricarbonyl iron complexes is described.

Diastereoselective elaboration of 2,3,4-substituted piperidines using diene iron tricarbonyl complexes. Total synthesis of (±)-dienomycin C and (±)-4-epi-dienomycin C

The diastereoselective formation of 2,3,4-substituted piperidines is achieved by condensation of the iron dienal complex 2 and the primary amine 3 via an intramolecular Mannich-type cyclisation. This method is illustrated by the first total synthesis of (±)-dienomycin C 1 and its C-4 epimer 9.

Synthesis and biological evaluation of analogues of M6G

Synthesis and biological evaluation of new derivatives of Morphine-6-Glucuronide (M6G) are described. M6G is an active metabolite of morphine which displays more analgesia than morphine with a superior side effect profile but with a less efficiently BBB penetration. These phenomena could be explained by the presence of the glucuronide moiety, which confers a higher hydrophilic character compare to morphine. In this context, we have prepared three analogues of M6G possessing a tetrazole, an oxadiazole, and a triazolopyrimidine moiety instead of the carboxylic acid function on position 5 of the sugar. These three analogues showed higher analgesic properties than morphine and M6G even by oral administration.

Stereoselective Synthesis of Substituted Piperidines – Total Synthesis and Absolute Configurations of (+)- and (–)-Dienomycin C

The first total asymmetric synthesis and the attribution of the absolute configurations of (+)-dienomycin C (1), an alkaloid isolated from a Streptomyces strain, are reported. This compound was prepared in six steps from the enantiopure tricarbonyl(dienal)iron complex (+)-4 which is easily obtained by separating preformed diastereomers, starting from phenylpentadienoic acid and (S)-methyl mandelate.

Asymmetric synthesis of alkaloid (–)-(2S,4S) SS 20846 A and its C-4 epimer

A diastereoselective intramolecular Mannich reaction using planar chiral iron dienal complexes is employed to prepare optically pure 2,4-disubstituted piperidines. This methodology is applied to the synthesis of natural alkaloids (–)-6 and (–)-7.