Synthesis, Reactivity, and Antibacterial Activity of -Difluoroalkene, Difluoromethyl, and Trifluoromethyl β-Lactams.

New -difluoroalkenes were synthesized by the dehydrofluorination of the corresponding 4-CF-β-lactams. An unexpected rearrangement mechanism of the ester moiety dependent on a stabilizing negative charge was observed. Hydrogenation to 4-CHF-β-lactams was successful from -difluoro-β-lactams.

Naphthalene vs. Benzene as a Transmitting Moiety: Towards the More Sensitive Trifluoromethylated Molecular Probes for the Substituent Effects.

The application of DFT computational method (B3LYP/6-311++G(d,p)) to mono- and poly(CF)substituted naphthalene derivatives helps to study changes in the electronic properties of these compounds under the influence of 11 substituents (-Br, -CF, -CH, -CHO, -Cl, -CN, -F, -NH, -NMe, -NO, and -OH) to confront substituent effects in naphthalene with an analogous situation in benzene. This paper shows the dependencies of theoretically calculated SESE (Substituent Effect Stabilization Energy) values on empirically determined, well-defined Hammett-type constants (, , , and ). Described poly(CF)substituted derivatives of naphthalene are, so far, the most sensitive molecular probes for the substituent effects in the aromatic system.

Deoxyfluorinating reagents as tools for γ-amino-α-hydroxyphosphonate modification.

Herein, we would like to present deoxyfluorinating reagents such as DAST and PyFluor and their successful use as tools for selective modification of γ-amino-α-hydroxyphosphonates. Depending on the deoxyfluorinating reagent applied, an intramolecular cyclization leading to phosphonates containing the 1,3-oxazinan-2-one moiety or direct nucleophilic deoxyfluorination yielding the α-fluorinated derivatives of γ-aminophosphonates was observed. The obtained compounds may be used as precursors in the preparation of medicinally important compounds , dipeptide analogues or scaffolds containing the 1,3-oxazinan-2-one group.

Highly Diastereoselective Construction of Carbon- Heteroatom Quaternary Stereogenic Centers in the Synthesis of Analogs of Bioactive Compounds: From Monofluorinated Epoxyalkylphosphonates to α-Fluoro-, β-, or γ-Amino Alcohol Derivatives of Alkylphosphonates.

The synthesis of the stable surrogates of an important amino acid ()-4-amino-3-hydroxybutyric acid (GABOB) such as substituted hydroxy aminophosphonic acids bearing a quaternary stereogenic center is presented. Highly diastereoselective formations of fluorinated spiroepoxy alkylphosphonate or related tertiary carbon-containing oxiranes from β-keto phosphonates possessing methyl, phenyl, or cyclohexenyl substituents, are reported. Stereoselective acid-promoted epoxide opening by bromide or azide followed by reduction/protection afforded tertiary bromides or -Boc derivatives of β-amino-γ-hydroxy alkylphosphonates in most cases, while the reactions of oxiranes with different amines yielded their β-hydroxy-γ-amino regioisomers.

Hypervalent-iodine mediated one-pot synthesis of isoxazolines and isoxazoles bearing a difluoromethyl phosphonate moiety.

A one-pot, regioselective 1,3-dipolar cycloaddition of in situ generated (diethoxyphosphoryl)difluoromethyl nitrile oxide toward selected alkenes and alkynes is reported. This protocol enables facile access to 3,5-disubstituted isoxazolines and isoxazoles bearing a CF2P(O)(OEt)2 moiety in good to excellent yields, under mild reaction conditions.

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates.

Herein, we present an efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates. Each step of the synthesis was optimized to provide excellent yields. Moreover, the absolute configuration of the obtained compounds was determined by X-ray analysis, which proved the stereochemistry that was proposed based on NMR studies.

Direct Access to Substituted 4-CF β-Lactams at the C-3 Position.

Mono- and disubstituted 4-CF β-lactams at the C-3 position have been obtained stereoselectively under basic conditions. A wide range of function such as alcohols, alkyls, aryls, esters, and double and triple bonds have been introduced.

Aromatic fluorocopolymers based on α-(difluoromethyl)styrene and styrene: synthesis, characterization, and thermal and surface properties.

A study on the α-(difluoromethyl)styrene (DFMST) reactivity under conventional radical copolymerization conditions is presented. Although the homopolymerization of DFMST failed, its radical bulk copolymerization with styrene (ST) led to the synthesis of fluorinated aromatic polymers (FAPs). The resulting novel poly(DFMST--ST) copolymers were characterized by H, F and C NMR spectroscopies that evidenced the successful incorporation of DFMST units into copolymers and enabled the assessment of their respective molar percentages (10.

Pyrrolidine and oxazolidine ring transformations in proline and serine derivatives of α-hydroxyphosphonates induced by deoxyfluorinating reagents.

Transformations of α-hydroxyphosphonates derived from proline or serine by treatment with different deoxyfluorinating reagents (DAST, Deoxofluor, PyFluor) are reported. Depending on the applied reagent, as well as the protecting group used (-Cbz, -Boc, -Bn) different types of products are observed. The reaction of -Cbz or -Boc prolinols with DAST or Deoxofluor due to aziridinium intermediate participation gave fluorinated amino phosphonates such as piperidine and pyrrolidine derivatives and/or oxazolidine-2-ones.

Functionalization of α-hydroxyphosphonates as a convenient route to -tosyl-α-aminophosphonates.

Direct conversion of the α-hydroxyl group by -toluenesulfonamide to yield α-(-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b-37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b-21a,b in the presence of KCO, the retro-Abramov reaction of the appropriate aldehydes, 1-5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b-37a,b with better diastereoselectivity than in the case of the Pudovik reaction.

Toward a physical interpretation of substituent effects: the case of fluorine and trifluoromethyl groups.

The application of ab initio and DFT computational methods at six different levels of theory (MP2/cc-pVDZ, MP2/aug-cc-pVTZ, B3LYP/cc-pVDZ, B3LYP/aug-cc-pVTZ, M06/cc-pVDZ, and M06/aug-cc-pVTZ) to meta- and para-substituted fluoro- and trifluoromethylbenzene derivatives and to 1-fluoro- and 1-trifluoromethyl-2-substituted trans-ethenes allowed the study of changes in the electronic and geometric properties of F- and CF3-substituted systems under the impact of other substituents (BeH, BF2, BH2, Br, CFO, CHO, Cl, CN, F, Li, NH2, NMe2, NO, NO2, OH, H, CF3, and CH3). Various parameters of these systems have been investigated, including homodesmotic reactions in terms of the substituent effect stabilization energy (SESE), the π and σ electron donor-acceptor indexes (pEDA and sEDA, respectively), the charge on the substituent active region (cSAR, known earlier as qSAR), and bond lengths, which have been regressed against Hammett constants, resulting mostly in an accurate correspondence except in the case of p-fluorobenzene derivatives. Moreover, changes in the characteristics of the ability of the substituent to attract or donate electrons under the impact of the kind of moiety to which the substituent is attached have been considered as the indirect substituent effect and investigated by means of the cSAR model.

[Chemical biology--a new branch of science].

Chemical biology is a new branch of science characteristic with global description of biological processes occurring within the cell. It covers synthesis of new chemical compounds for systems biology studies and search for natural small molecular weight chemical compounds with high cellular regulatory potential. Chemical biology power is based on 3 pillars as chemical synthesis, computer calculations and systems biology.

Simple synthesis of some pentafluoropropenyl derivatives of pyrimidine and purine based on addition-elimination reaction.

Various pentafluoropropenyl derivatives of pyrimidine and purine bases have been obtained in good to high yield. The procedure involves the reaction of appropriate lithium derivatives prepared from both electron-rich and electron-poor pyrimidines, with the hexafluoropropene at a low temperature, via an addition-elimination process. Organolithiums of pyrimidine and purine bases give addition-elimination products as E/Z mixtures, whereas the products of the reaction of lithium amide of protected inosine with hexafluoropropene contain traces of an addition product as well as the stable perfluoroenamine.

[Level of cadmium and zinc in placenta of smoking women].

One possible mechanism of lowering of the birth weight by tobacco smoke is disturbance in zinc transfer trough placenta caused by accumulation of cadmium in placenta. The aim of the study was determination of cadmium and zinc in placenta of smoking women and correlation its with cotinine concentration and birth weight The study shown that concentration of cotinine in urine of smoking woman was 859+/-1234 ng/mg creatinine. Cadmium and zinc concentrations in smokers were higher (Cd 0.

[Determination of cadmium in urine of tobacco smoking pregnant women].

Tobacco smoke contain few thousands of chemical compounds, among them heavy metals. From toxicological point of view most important are lead, cadmium and radioactive polonium 210. The aim of the study was determination of cadmium in urine of tobacco smoking pregnant woman and checking if there is a correlation between the concentration of cadmium and cotinine, the most frequently used tobacco smoke biomarker.