Alain Ahond

Homophymine A, an Anti-HIV Cyclodepsipeptide from the Sponge Homophymia sp

A new anti-HIV cyclodepsipeptide, homophymine A, was isolated from a New Caledonian collection of the marine sponge Homophymia sp. The structure of homophymine A was determined by interpretation of spectroscopic data, acid hydrolysis, and LC-MS analysis. Homophymine A contains 11 amino acid residues and an amide-linked 3-hydroxy-2,4,6-trimethyloctanoic acid moiety. Along with four D-, two L-, and one N-methyl amino acids, it also contains four unusual amino acid residues: (2S,3S,4R)-3,4-diMe-Gln, (2R,3R,4S)-4-amino-2,3-dihydroxy-1,7-heptandioic acid, L-ThrOMe, and (2R,3R,4R)-2-amino-3-hydroxy-4,5-dimethylhexanoic acid. In a cell-based XTT assay, homophymine A exhibited cytoprotective activity against HIV-1 infection with a IC50 of 75 nM.

Seasonal variation of neutral and basic taxoid contents in shoots of European Yew (Taxus baccata)

Abstract Seasonal variations of taxoid constituents were determined in shoots of European Yew collected from two locations. The first samples originated from a male Taxus baccata tree growing in Gif, France. The second samples were obtained from genetically identical female Irish Yew trees ( T. baccata var. fastigiata ), of the same age and growing at one site in Dublin, Ireland. Shoots were collected monthly for one year and separated into needles and stems. Neutral taxoids (paclitaxel and 10-deacetylbaccatin III (10-DAB III)) and basic taxoids (including taxines B) were extracted and quantified. Needles yielded significantly higher levels of taxoids than stems. 10-DAB III contents in needles of French samples showed considerable monthly fluctuations, while in needles of the Irish samples maximum yields of 10-DAB III were found in June. Highest levels of paclitaxel were present between February and April. Basic taxoids occurred in highest concentrations (total alkaloids 9.49 g/kg) in the August collection of French samples, but in needles of the Irish Yew in November and December (total alkaloids 16.9 g/kg; taxines B 10.9 g/kg). No conclusion could be drawn as to the optimum time of year for harvesting, since this varies from tree to tree, depending on T. baccata variety, location and taxoid type.

Synthèse de métabolites marins 2-aminoimidazoliques: Hyménidine, oroïdine et kéramadine

Abstract Through a general synthetic scheme, hymenidin, oroidin and keramadine, all marine 2-aminoimidazole metabolites were prepared. Seven steps from imidazolemethanol provided an improved synthesis of oroidin and the first synthesis of hymenidin and keramadine.

Étude par rm13c d'alcaloïdes à squelette acridinone 9(10h) et pyrido(4,3b) carbazole(6h)

Resume Des alcaloides naturels et synthetiques de type acridinone et pyridocarbazole ont ete etudies par RMN du carbone ainsi que des molecules plus simples utilisees comme modeles.

Taxoïdes: 7-Déshydroxy-10-acétyldocétaxel et nouveaux analogues préparés à partir des alcaloïdes de l'If

Abstract Three new 7-deoxydocetaxel derivatives have been prepared from natural taxine B and isotaxine B: the first one, 2-debenzoyl-9-dihydro-1,2-O-benzylidene-9,10-O-isopropylidene-7-deoxydocetaxel has a slight cytotoxicity and a weak microtubule disassembly inhibitory activity; the other two derivatives, 9-dihydro-9,10-O-isopropylidene-7-deoxydocetaxel and 7-deoxy-10-acetyldocetaxel are cytotoxic and reveal a good microtubule disassembly inhibitory activity.

Synthèse des 1-amidopyrrolizidines naturelles, absouline et laburnamine, de dérivés et d'analogues pyrrolidinoimidazoliques

Resume Natural 1-amidopyrrolizidines, absouline and laburnamine, were synthesized via stable pyrrolizidin-1-one hydrobromide. Amides, ester derivatives and aminopyrrolidinoimidazole analogues were also prepared and their biological activities tested.

Synthesis of the marine carbinolamine (+/−) longamide control of N-1 and C-3 bromopyrrole nucleophilicity

A short synthesis of (+/−) longamide 1 using a probable biomimetic cyclisation of 12 is described. The separation of its enantiomeric forms and their racemisation are examined. The ring-chain tautomerism involving a potential nucleophilicity of N1/C3 of bromopyrrole compounds has been examined. The behaviour of 7 in protic mild or in vigorous acidic conditions provides an entry to regioselective synthesis of marine polycycle alkaloids such as 2, 3, and 4. A biogenetic pathway is proposed for polycyclic 2-aminoimidazolopyrrole marine metabolites.

Taxoïdes: Nouveaux analogues du 7-déshydroxydocétaxel préparés à partir des alcaloïdes de l'If

Abstract Two new 7-deoxydocetaxel derivatives have been prepared from natural taxine B and isotaxine B: 2-debenzoyl-9-dihydro-1,2,9,10-O-acetonide-7-deoxydocetaxel and 2-debenzoyl-1,2-O-acetonide-7-deoxy-10-acetyldocetaxel None of the compounds is cytotoxic; the second one, bearing one acetonide reveals a very weak microtubule disassembly inhibitory activity.

Girolline: A Potential Lead Structure For Antiplasmodial Drug Research

Girolline is a 2-aminoimidazole derivative extracted from Cymbastela cantharella (a New-Caledonian sponge) that has shown antitumor activity. In this study, we investigated its antimalarial activity and the point of action within the erythrocytic cycle of Plasmodium falciparum. Initially, we tested girolline and some synthetic analogues in vitro against four P. falciparum strains. The IC (50) values of girolline ranged from 77 to 215 nM, and as with artemisinin or chloroquine, girolline inhibited parasitic growth by 100 %. Girolline was found to be active at a dose of 1 mg/kg/d (orally and intraperitoneally) in vivo. Moreover, there was a significant synergistic effect between girolline and chloroquine in vitro. The investigation of the mechanism of action of girolline during the erythrocytic life cycle of the parasite showed that its action targets the synthesis of proteins by the parasite. With such a biological profile, girolline could be considered as a model chemical structure for new candidates in the arsenal of new drugs and in particular of drugs able to fight malaria.

Evaluation of taxoids from Taxus sp. crude extracts by high performance liquid chromatography

Abstract The extraction procedures and analysis methods by high-performance liquid chromatography (HPLC) for taxine B (1), isotaxine B (2) and 10-deacetylbaccatin III (3), expected or already known “precursors” of paclitaxel or active analogues, were developed for in series analyses of Taxus needles.