Michel Klich

Tosylates in palladium-catalysed coupling reactions. Application to the synthesis of arylcoumarin inhibitors of gyrase B

Abstract The palladium-catalysed coupling reaction between tosylate derivatives and organostannanes has been investigated as a methodology for carbon–carbon bond formation. Aryl substituents have been successfully incorporated even in highly functionalised coumarin structures to afford new analogues of the antibiotic novobiocin.

Synthese de n-(tetrazol-5-yl) azetidin-2-ones

Resume N-(tetrazo1-5-y1 ) azetldin-2-ones can be conveniently prepared by reacting N-unsubstituted beta-lactams with 1-benzyl 5-fluoro 1H-tetrazole

Synthesis and biological evaluation of coumarincarboxylic acids as inhibitors of gyrase B. L-rhamnose as an effective substitute for L-noviose

A series of novobiocin-like coumarincarboxylic acids has been prepared bearing the L-rhamnosyl moiety as the sugar portion of the molecule. The similar DNA gyrase inhibitory activity of the novel class of coumarins to that of novobiocin demonstrates that L-rhamnose can effectively replace L-noviose. Introduction of alkyl side-chains at C-5 of coumarin leads to improved in vitro antibacterial properties in the novel series.

Synthesis of a fluorescent steroid derivative with high affinities for the glucocorticoid and progesterone receptors

The synthesis of RU 45196, an 11 beta-substituted 19-norsteroid of the estra-4,9-diene series, incorporating the nitrobenzoxadiazole (NBD) fluorophore, is reported. The highly fluorescent target compound displayed remarkable affinity for both the progesterone and glucocorticoid receptors. The present work demonstrates for the first time that it is indeed possible to design fluorescent steroid conjugates which maintain very high affinities for their cognate receptors and which are potentially useful for mechanistic and diagnostic purposes.

Stereoselective synthesis of 5-monoalkyl and 5,5-dialkylsubstituted noviose derivatives

Abstract The stereoselective synthesis of 5-monosubstituted and 5,5-dialkylsubstituted noviose derivatives has been achieved starting from l -arabinose. These noviose derivatives could be used as useful building blocks in probing structure–activity relationships (SAR) of coumarin antibiotics that are inhibitors of DNA gyrase.

Synthesis of isothiochroman 2,2-dioxide and 1,2-benzooxathiin 2,2-dioxide gyrase B inhibitors

Abstract The design, synthesis and in vitro biological evaluation of isothiochroman 2,2-dioxide and 1,2-benzooxathiin 2,2-dioxide analogues of coumarin inhibitors of gyrase B are described. Compared to coumarin derivatives, compounds of the 1,2-benzooxathiin 2,2-dioxide series display improved inhibitory potency in negative supercoiling of relaxed DNA gyrase.

Synthese de N-(tetrazol-5-yl) azetidin-2-ones

Abstract The title compounds were obtained by addition of a glycine enolate to a N-(tetrazol-5-yl) imine followed by cyclisation. This route provided both the cis and the trans substituted azetidinones. The cis compounds possessed improved antibiotic activity as compared to the trans counterparts.

Synthesis of an N-(tetrazol-5-yl) azetidin-2-one from L-tartaric acid

Abstract L (+) tartaric acid was a useful starting synthon to obtain N -(tetrazol-5-yl) azetidin-2-ones.

Synthese d'un isostere soufre de la prostaglandine A2

Abstract The synthesis of the title compound 2a , a prostaglandin with a β-thiolactone ring is described, which involves the use of 2-tetrahydropyranthiol, an efficient reagent for introducing the sulfur atom.