Michel Koch

A new synthetic access to furo[3,2-f]chromene analogues of an antimycobacterial

From the structure of 3,3-dimethyl-3H-benzofuro[3,2-f][1]-benzopyran, a selective in vitro inhibitor of mycobacterial growth, we have undertaken a structure-activity relationship investigation. We wish to report here our results on the use of [2+3] cycloadditions between 2-formylbenzoquinone and various enol derivatives to give various 4-formyl-5-hydroxy benzofurans. In the next step, an ytterbium triflate-catalysed reaction with 2-methylpropene allowed the preparation of various original furo[3,2-f]chromenes derivatives. Their biological evaluation on the growth of Mycobacterium smegmatis as well as Mycobacterium tuberculosis pointed out that some analogues were four times more active than the initial hit.

Diversity-oriented synthesis of furo[3,2-f]chromanes with antimycobacterial activity

We previously reported the synthesis and the antimycobacterial activity of 4-(7,7-dimethyl-7H-furo[3,2-f]chromen-2-yl)pyridine. From this result, we sought to design simple synthetic accesses to related structures allowing the preparation of a diverse set of analogues. Two approaches were investigated. From 3-(2-bromo-7,7-dimethyl-8,9-dihydro-7H-furo[3,2-f]chromen-1-yl)propyl acetate, we prepared 2-arylated derivatives via Suzuki-Miyaura reactions between this bromine-bearing compound and various arylboronates. Moreover, and even more simple, we prepared the ((6-hydroxy-2,2,7,8-tetramethylchroman-5-yl)methyl)triphenylphosphonium salt via a selective bromination of 2,2,5,7,8-pentamethylchroman-6-ol. From this salt, a two stage Wittig reaction with an array of activated acids allowed the quick preparation of many analogues. The biological evaluation of the effect of these compounds on the growth of Mycobacterium bovis as well as Mycobacterium tuberculosis pointed out a fourfold improvement of the antimycobacterial properties for one of the compounds made. However, the many analogues which inhibited the growth of M. tuberculosis in the 0.6-5 microg/mL range turned out to be also cytotoxic on VERO cells growth at the same concentration range.

Feretoside et gardenoside du Feretia apodanthera: rmn du carbone 13 en série iridoide

Abstract The 13 C NMR spectra of some iridoids of known structure are analysed. The data obtained have been applied to the determination of structure of feretoside and the identification of gardenoside, both isolated from the stem bark of Feretia apodanthera .

Chalconoid and stilbenoid glycosides from Guibourtia tessmanii

Phytochemical studies on the stem bark of Guibourtia tessmanii yielded a dihydrochalcone glucoside, 2,4-dihydroxy-4-methoxy-6-O-beta-glucopyranoside dihydrochalcone and a new stilbene glycoside, 3,5-dimethoxy-4-O-(beta-rhamnopyranosyl-(1-->6)-beta- glucopyranoside) stilbene besides the known pterostilbene. Their structures were established on the basis of one and two dimensional NMR spectroscopic techniques, FABMS and chemical evidence.

A Novel Synthesis of 6-Demethoxyacronycine

The title compound was synthetized in six steps, starting from 3-nitrophenol. The key-step involves condensation of 2-bromobenzoic acid with 5-amino-2,2-dimethylchromene

L'oxo-17 ellipticine, nouvel alcaloide de strychnos dinklageI

Resume The structure of 17-oxo ellipticine 1 has been established by spectral analysis and chemical correlation with ellipticine, and its biosynthesis and chemotaxonomic significance are discussed.

CINQ alcaloides nouveaux de Strychnos henningsii

Abstract Five new alkaloids have been isolated from the leaves and stems of Strychnos henningsii : tsilanimbine, N a -desacetyl-17- O -acetyl-18-hydroxyisoretuline, 18-hydroxyisoretuline, N a -desacetylisoretuline and N a -desacetyl-18-hydroxyisoretuline. The two latter, unknown as natural products, have already been obtained by degradation of strychnine.

Homochiral rigid γ-amino acid glycosides from aucubin

Two homochiral glucosylated hydroxy γ-amino acids 7 and 11 were synthesized by chiral pool synthesis in eight steps from the natural iridoid aucubin.

An efficient synthesis of optically active 4-demethoxy anthracyclinones

Abstract Optically active 4-demethoxy-anthracyclinones were synthezised in few steps from lactose as chiral precursor of ring A and from leucoquinizarine as precursor of rings B, C and D.

A novel series of cytotoxic iridoid glucosides derived from aucubin: Design, synthesis and structure–activity relationships

Five new unsaturated iridolactones 3-7 related to natural cytotoxic oxylipins, Tei 9826, and iridolactone 2, were prepared by parallel synthesis from natural aucubin. It was found that perpivaloyl iridoid glucosides 2, 3, and 4 were markedly cytotoxic against both L1210 and KB-3-1 cell lines.