Synthetic and Mechanistic Study of the Catalytic Enantioselective Preparation of Primary β‑Amino Ketones from Enones and a Fluorinated Gabriel Reagent

The salen μ-oxo complex of aluminum <b>1</b> catalyzes the asymmetric 1,4-addition of the novel ammonia equivalent 3,4,5,6-tetrafluorophthalimide to unsaturated ketones. All of the reagents are inexpensive and are readily available. The products are formed in up to 89% yield and up to 96% ee. The tetrafluorophthalimide group is removed under mild chemoselective conditions and in high yields to afford the free primary amines. Mechanistic studies suggest that the reaction occurs through a dual activation mechanism. A pre-equilibrium formation of a 1:1 complex between tetrafluorophthalimide and the catalyst is observed. The rate-determining step is the addition of tetrafluorophthalimide catalyst complex to the catalyst activated enone. These mechanistic studies provide important clues for the further development of catalytic asymmetric reactions

Maša Mlinarič - Forma v gibanju

Mrežno ali geometrijsko naravnani prostor slikovnega polja in njegov »podaljšek« v razširjeno sliko – v slikarski objekt (B. Riley, V. Richter, D. Jejčič), se v povezovalnem študijskem procesu formira najprej kot izkušnja z risbo in nato kot slikarska izkušnja. Oboje se ob izpitu nato vzporedno artikulira v znanju, s široko oporo likovne teorije (V. Vasarelly- Op Art in entnografska povezava z tradicionalnimi vezeninami), s področjem umetnostne zgodovine ter z drugimi povezavami, kot je prostorsko oblikovanje ali področje glasbe (P. Mondrian-»Bugi Wugi«) ali skozi signalistično poezijo (Zagoričnik-»West Est«), ki se nato kot refleksija izgovarja kot priprava v učnih načrtih

Enolonium Species-Umpoled Enolates

Enolonium species/iodo(III) enolates of carbonyl compounds have been suggested to be intermediates in a wide variety of hypervalent iodine induced chemical transformations of ketones, including α-C-O, α-C-N, α-C-C, and alpha-carbon- halide bond formation, but they have never been characterized. We report that these elusive umpoled enolates may be made as discrete species that are stable for several minutes at-78 degrees C, and report the first spectroscopic identification of such species. It is shown that enolonium species are direct intermediates in C-O, C-N, C-Cl, and C-C bond forming reactions. Our results open up chemical space for designing a variety of new transformations. We showcase the ability of enolonium species to react with prenyl, crotyl, cinnamyl, and allyl silanes with absolute regioselectivity in up to 92% yield

Novel Water-Soluble Amphotericin B‑PEG Conjugates with Low Toxicity and Potent <i>in Vivo</i> Efficacy

Systemic fungal infections are an increasingly prevalent health problem, especially among immunocompromised patients. Antifungal drug development lags far behind in comparison to other types of antimicrobial drugs. Current commercially available antifungals are limited by their insufficient potency, side effects, drug–drug interactions, developing drug-resistance, and narrow formulation options. Here, we report the preparation and evaluation of two novel PEG amide conjugates of amphotericin B (AMB (<b>1</b>)): AB1 (<b>4</b>) and AM2 (<b>5</b>). These compounds are nonlabile, they are prepared in only two and three synthetic steps, respectively, and they show antifungal activity against a wide range of clinical fungal isolates. Their toxicity is significantly lower, and their water solubility is up to 5000-fold higher than that of AMB (<b>1</b>). <i>In vivo</i> efficacy studies in a mouse model of systemic candidiasis showed that AM2 (<b>5</b>) successfully cured all the mice at concentrations above 3.5 mg/kg body weight. In conclusion, these properties make AB1 (<b>4</b>) and AM2 (<b>5</b>) promising candidates for clinical use

α‑<i>N</i>‑Heteroarylation and α‑Azidation of Ketones via Enolonium Species

Enolonium species, resulting from the umpolung of ketone enolates by Koser’s hypervalent iodine reagents activated by boron trifluoride, react with a variety of nitrogen heterocycles to form α-aminated ketones. The reactions are mild and complete in 4–5 h. Additionally, α-azidation of the enolonium species takes place using trimethylsilyl azide as a convenient source of azide nucleophile

Transition-Metal-Free Intermolecular α‑Arylation of Ketones via Enolonium Species

Herein it is shown, for the first time, that enolonium species are powerful electrophiles capable of reacting with aromatic compounds in an intermolecular manner to afford α-arylated ketones. The reaction is compatible with a variety of functional groups, is of wide scope with respect to aromatic compounds and ketone, and even works for polymerization-prone substrates such as substituted pyrroles, thiophenes, and furans. Only 1.6 to 5 equiv of the commodity aromatic substrates is needed