Stéphane Lebrun

Hemisynthesis of all the O-monomethylated analogues of quercetin including the major metabolites, through selective protection of phenolic functions

Abstract A new methodology for the hemisynthesis of all the five O-monomethylated analogues of quercetin (3′-O-methylquercetin (isorhamnetin), 4′-O-methylquercetin (tamarixetin), 3-O-methylquercetin, 5-O-methylquercetin (azaleatin) and 7-O-methylquercetin (rhamnetin)) through sequential protection of the different phenolic functions of quercetin is reported.

TOTAL SYNTHESES OF ()-CRYPTOPLEURINE, ()-ANTOFINE AND ()-DEOXYPERGULARININE

Abstract The alkaloids (±)-cryptopleurine 1 , (±)-antofine 2 , and (±)-deoxypergularinine 3 were synthesized by Pictet-Spengler cyclization of the 2-arylmethylpiperidine and -pyrrolidines 4, 5 and 6 obtained by sequential N -deprotection-reduction of the parent enecarbamates 7, 8 and 9 . These latter were made by the Horner reaction of phosphorylated carbamates 12 and 13 with the appropriate aldehydes 10 and 11 .

Characterization of methylation site of monomethylflavan‐3‐ols by liquid chromatography/electrospray ionization tandem mass spectrometry

Liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was used for the structural characterization and differentiation of four isomeric O-monomethylated catechins (on phenolic positions) by the analysis of the fragmentation behaviour of catechin. The catechin fragmentation routes were rationalized and it is shown that several diagnostic ions such as (1,3)A(+), (1,2)B(+), and (1,4)B(+) allow the unambiguous identification of the methylated ring. The precise position of the methyl group on each ring is determined by the difference in the relative intensities of the diagnostic ions. Isomeric O-methylepicatechins were also differentiated using this methodology.

Dramatically different photochemical behaviour of 1-aroyl-2-methylene piperidine and pyrrolidine derivatives. An expeditious synthesis of ruspolinone

Abstract Upon irradiation in neutral solvent, the diversely substituted 1-aroyl-2-methylenepiperidines 6a-f give rise to photocyclized products 4a-f while their pyrrolidine congeners 7a,c,d afford enaminoketones 18a,c,d products of photo-Fries rearrangement.

Asymmetric synthesis of 5-arylmethylpyrrolidin-2-ones and 2-arylmethylpyrrolidines

Abstract An efficient methodology for the enantioselective synthesis of 5-arylmethylpyrrolidin-2-ones and 2-arylmethylpyrrolidines has been devised. The key step is the stereoselective hydrogenation of the N -acylhydrazonium salts obtained from the corresponding arylmethylene hydrazides. These highly conjugated compounds are readily prepared by reacting a chiral succinimide with a variety of arylmethyl Grignard reagents. Removal of the chiral auxiliary and subsequent reduction complete the synthesis of the title compounds.

First synthesis and pharmacological evaluation of benzoindolizidine and benzoquinolizidine analogues of α- and β-peltatin

Abstract The benzoindolizidine and-quinolizidine analogues of α- and β-peltatin were designed and synthesized by two different synthetic routes involving as the key step the Bischler–Napieralski cyclization of suitably substituted N -acyl-2-arylmethylpyrrolidine and -piperidine derivatives. The in vitro biological activity of these analogues as well as some of their derivatives was subsequently evaluated.

First total synthesis of cichorine and zinnimidine

The first total synthesis of the phytotoxins cichorine and zinnimidine is described. The synthetic tactics involve the sequential connection of the dense and diverse functionalities on the aromatic nucleus followed by a Parham cyclization process, giving rise to the lactam unit embedded in the title compound framework.

Asymmetric synthesis of (+)- and (−)-latifine

Abstract A concise and novel synthesis of isoquinoline alkaloids ( S )-latifine and of its antipode is reported. The key step relies on the stereoselective reduction of an appropriately substituted diarylenamine equipped with a chiral auxiliary followed by Pictet–Spengler cyclization to generate the tetrahydroisoquinoline unit.

A new synthesis of (+)- and (−)-cherylline

A new and concise synthesis of enantiopure antipodes of alkaloid cherylline has been devised. The synthetic strategy relies upon the reduction of a diversely and polyprotected diarylenamine bearing a chiral auxiliary. Separation of diastereopure intermediates, concomitant deprotections and intramolecular reductive amination complete the synthesis of the natural (S)-enantiomer and of the unnatural (R)-configured antipode.

Selective protection of catechin gives access to the intrinsic reactivity of the two phenol rings during H-abstraction and photo-oxidation

Abstract Selective protection of the catechol ring of catechin has been achieved. From this key compound, catechin analogues protected either on the catechol or the resorcinol rings were synthesized. From these analogues, phenoxyl radicals on the catechol or on the resorcinol rings were produced by photo-oxidation (direct irradiation at 308 nm) of the phenolate and by H-abstraction experiments. Spectra of the radicals were recorded at short times before any further chemical evolution. Investigation of catechin behavior itself and comparison with the reactivity of models show that H-abstraction is unselective, whereas photo-oxidation is selective on the catechol ring monoanion establishing that this ring has the lowest pKa.