The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors

Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the molecules with specifically positioned fluorine atoms in order to control the molecular conformations. The fluorinated analogs were screened against a panel of 11 HDAC isoforms, and minor differences in isoform selectivity patterns were observed.

Tackling Pristinamycin IIB Problems: Synthetic Studies toward Some Fluorinated Analogs

Streptogramins are potent antibiotics against numerous highly resistant pathogens and therefore are used in last-resort human therapy. These antibiotics are formed of both A- and B-group compounds named pristinamycins that differ in their basic primary structures. Although pristinamycin IIB is among the most interesting antibiotics in this family, it presents numerous problems related to its chemical structure, such as instability at most pH levels, weak solubility in water, and resistance by bacteria. As a response to the need for developing new antimicrobial agents, we have designed a new analog of pristinamycin IIB, based most importantly on the introduction of fluorine atoms. We conjectured indeed that the introduced modifications may solve the above-mentioned problems exhibited by pristinamycin IIB. Our multistep synthetic approach relies on few key reactions, namely a Wittig reaction, a Grubbs reaction, and dihydroxy, -difluoro API (Advanced Pharmaceutical Intermediate) synthesis

HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes

In the present work, the employment of fluorinated alcohols, specifically 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), as solvent and promoter of the catalyst-free synthesis of substituted tetrahydrofuranes through the addition of electron-rich alkenes to epoxydes is described. The unique properties of this fluorinated alcohol, which is very different from their non-fluorinated analogs, allows carrying out this new straightforward protocol under smooth reaction conditions affording the corresponding adducts in moderate yields in the majority of cases. Remarkably, this methodology has allowed the synthesis of new tetrahydrofuran-based spiro compounds as well as tetrahydrofurobenzofuran derivatives. The scope and limitations of the process are also discussed. Mechanistic studies were also performed pointing towards a purely ionic or a SN2-type process depending on the nucleophilicity of the alkene employed.

Diastereoselective synthesis and conformational analysis of 4,5-difluoropipecolic acids

Stereoselectively-fluorinated analogs of pipecolic acid have been investigated through a combined theoretical and experimental approach.

Temperature Dependence of the Bulk Elasticity Modulus of Aliphatic Alcohols and Their Fluorinated Analogs

The density of some fluorinated and non-fluorinated normal monoatomic alcohols and the sound propagation velocity in them have been studied experimentally in a temperature interval of 293–363 K. The bulk modulus of elasticity is calculated, and its relation with the intermolecular interaction energy is analyzed. The energy of intermolecular interaction in fluorinated alcohols is shown to be lower than in their non-fluorinated analogs. The substitution of hydrogen atoms by fluorine ones in the molecules of aliphatic alcohols increases the equilibrium distance between the molecules.