ABSTRACT
The reactions of the ring-contracted aldehydes, derived from anhydrodihydroartemisinin, with gem-difluoroenoxysilanes in the presence of BF(3).Et(2)O afforded the corresponding difluoromethylene ketol adducts in good yields. Similar Lewis acid catalyzed reactions of dihydroartemisinin acetate with the difluoroenoxysilanes provided the 10-substituted difluoromethylene ketones in good to moderate yields. Interestingly enough, the course and the stereochemistry of these reactions are highly dependent on the nature of the Lewis acids used; the addition reaction was accompanied by epimerization at C-9, and the stereochemistry at C-10 depends on the difluoroenoxysilane used. The best results were obtained using SnCl(4) to give the 9alpha,10beta-stereoisomer in high stereoselectivity. When 0.4 equiv of SnCl(4) was used for the reaction with the alpha-(4-methoxyphenylenoxysilane)-beta,beta-difluoroenoxysilane, however, a rearrangement of the endoperoxide was observed.
Subject(s)
Artemisinins , Drugs, Chinese Herbal/chemistry , Fluorenes/chemistry , Ketones/chemistry , Methane/analogs & derivatives , Methane/chemistry , Sesquiterpenes/chemistry , Animals , Antimalarials/chemical synthesis , Antimalarials/chemistry , Drugs, Chinese Herbal/chemical synthesis , Hydrocarbons , Plasmodium falciparum/drug effects , Sesquiterpenes/chemical synthesisABSTRACT
[reaction: see text] alpha-Benzyloxy alpha-CF(3)-beta-lactams are shown to offer the first examples of the enolate [1,2]- and enolate ortho-[2,3]-Wittig rearrangements which provide a unique entry to the alpha-benzyl-alpha-hydroxy lactams and the alpha-aryl-alpha-hydroxy lactams, respectively. Both products are potential precursors of new trifluoromethyl isoserines, and the latter is not accessible via the usual alkylation methodology.
Subject(s)
beta-Lactams/chemistry , Alkylation , Indicators and ReagentsABSTRACT
A concise preparation of tetrasubstituted hindered functionalized CF3-olefins 2-7 from corresponding enol ether 3 is described. Geometrically pure gamma-CF3, gamma-alkyl allylic alcohols thus prepared could undergo Claisen-type rearrangements and provide, in good yields, carboxylic esters and amides containing a beta- quaternary CF3-substituted carbon.
ABSTRACT
This paper describes the optimization of the preparation of ciprofloxacin-loaded polyethylbutylcyanoacrylate (PEBCA) nanoparticles. The association of ciprofloxacin with nanoparticles was performed by emulsion polymerization, but successful entrapment was only obtained in the presence of acetone in the polymerization medium. This preparation process led to a stable ciprofloxacin nanoparticle suspension, with a mean size value twice as high as that obtained in the absence of drug, and an association efficiency of 82%. Moreover, the molecular weight value of ciprofloxacin nanoparticles was shown to be reduced as compared with unloaded nanoparticles. Drug release from the colloidal carrier in medium containing esterase was found to be very slow (a maximum of 51.5% after 48 h), suggesting that this release resulted from bioerosion of the polymer matrix. Interestingly, it was observed that 30.5% of the initial amount of ciprofloxacin was not detectable by HPLC analysis after nanoparticle preparation and corresponded either to ciprofloxacin covalently bound to PEBCA or to ciprofloxacin chemically degraded during the polymerization process. 19F-NMR analysis demonstrated that ciprofloxacin entrapped into nanoparticles was only in its neutral form. The measurements of molecular weight suggest the participation of the antibiotic as an anionic polymerization initiator, leading to the formation of a chemical bond between some of the drug and the polymer. These data allowed us to propose a model describing the association of ciprofloxacin with PEBCA nanoparticles obtained by emulsion polymerization.
