Synthesis of unusual amino acids: N-(tert-butoxycarbonyl)-L-vinyl glycine and N-(tert-butoxycarbonyl)-L-homophenylalanine

The synthesis of the unusual amino acids N-(tert-butoxycarbonyl)-L-vinyl glycine and N-(tert-butoxycarbonyl)-L-homophenylalanine starting from commercially available D-xylose via an alkylative fragmentation method is described

An expeditious approach for the synthesis of optically active allyl alcohols

Aldehyde tosylhydrazones having an adjacent O̲-isopropylidene group undergo a condensation-fragmentation process in the presence of alkyl magnesium and alkyllithium reagents to yield chiral allyl alcohols

Alkylative elimination of α,β-epoxy tosylhydrazones

Optically pure allyl alcohols have been prepared from tosylhydrazones derived from chiral epoxy aldehydes by alkylative elimination utilizing alkyl magnesium reagents

Variability of composition and effects of essential oils from Rhanterium adpressum Coss. & Durieu against mycotoxinogenic Fusarium strains

International audienceThe antifungal potency of the essential oils of Rhanterium adpressum was evaluated against four mycotoxigenic strains of the genus Fusarium. The essential oils were obtained, separately, by hydro-distillation of the aerial parts of R. adpressum (leaves and flowers). The parts were collected during the period of bloom (3 months) for 3 years. The GC-MS analysis revealed thirty-six compounds for the essential oils, divided into four classes of chemical compounds, with variable percentages according to the month of extraction. The monoterpene hydrocarbons form the main class in these oils. On the other hand, the highest percentages of the oxygenated compounds are observed in the samples collected during the month of May. The direct contact method was used to evaluate the antifungal activity of the essential oils. The activity can be attributed to their relatively high composition of oxygenated monoterpenes. Flowers extract showed strong inhibitory activity, with very interesting concentrations of IC50 and MIC for both tests on solid and liquid medium. The effect of these oils on the production of type B trichothecenes (TCTBs) was evaluated, showing a significant inhibitory effect on TCTBs production, for both extracts (leaves and flowers). The rates of inhibition were 66-97 and 76-100% of FX, 3-ADON and 15-ADON, respectively. The inhibition of fungal biomass and the production of TCTBs depended on the used concentration of the essential oils. These results suggest that the essential oils from R. adpressum are able to control the growth of the tested strains and their subsequent production of TCTB mycotoxins

Structural Studies of an Impurity Obtained During the Synthesis of Telithromycin Derivatives

In an effort to synthesize a key intermediate, for synthesis of a variety of telithromycin derivatives a new by-product has been formed at the third stage of the synthetic scheme. The starting material, Clarithromycin, on treatment with hydrochloric acid and on benzoylation resulted in the formation of (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-4,12,13-trihydroxy-7-methoxy- 3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecan-6-yl 3,4,6-trideoxy- 3-(dimethylamino)-2-O-(phenylcarbonyl)-β-D-xylo-hexopyranoside (2). Oxidation of this gave (3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy- 7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradecan-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O-(phenylcarbonyl)-β-D-xylo-hexopyranoside (3), and also an unexpected by-product 4 in equivalent amounts. The O21–H hydroxyl group in 3 was mesylated with dimethyl sulphoxide (DMSO) in pyridine leading to the precursor (3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl- 12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-12-(methylsulfinyl)- 2,4,10-trioxooxacyclotetradecan-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O- (phenylcarbonyl)-β-D-xylo-hexopyranoside (5), which on further treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone and methylene chloride resulted in the formation of intermediate 6. The by-product 4 and the intermediate 6 were isolated and characterized as (1S,2R,5R,7R,8R,9R)-2- ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6-dioxo-3,15-dioxabicyclo[10.2.1]- pentadeca-11,13-dien-8-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O-(phenylcarbonyl)- β-D-xylo-hexopyranoside (4) and (3R,5R,6R,7R,9R,11E,13S,14R)-14- ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec- 11-en-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O-(phenylcarbonyl)-β-Dxylo- hexopyranoside (6) respectively by 2D NMR and single crystal X-ray diffraction

Novel and potent oxazolidinone antibacterials featuring 3-indolylglyoxamide substituents

Novel oxazolidinone antibacterials bearing a variety of 3-indolylglyoxamide substituents have been explored in an effort to improve the spectrum and potency of this class of agents. A subclass of this series was also made with the diversity at C-5 terminus. These derivatives have been screened against a panel of clinically relevant Gram-positive pathogens and fastidious Gram-negative organisms. Several analogs in this series were identified with in vitro activity superior to linezolid (MIC = 0.25-2 μg/mL). Compounds 10a, 10c, 10e and 10f displayed activity against linezolid resistant Gram-positive organisms (MIC = 2-4 μg/mL). Selected oxazolidinones were evaluated for in vivo efficacy against a mouse systemic infection model