A new efficient procedure for the synthesis of 1-hydroxymethylene-1,1-bisphosphonate monomethyl esters in three steps from acid chlorides is reported here.
We previously reported a simple and efficient one-pot procedure for synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids (HMBP). According to this method, we synthesized a series of new aromatic HMBP and investigated structure-activity relationships by evaluating their anti-proliferative activity against A431 human tumor cell line. Our results showed that the introduction of an extra methylene group in a pyridyl-containing R2 side chain increased 100-fold the anti-proliferative activity of the HMBP. In contrast, this chemical modification did not modify the anti-proliferative activity of compounds substituted with a phenyl-containing R2 side chain. Para-substitution of the phenyl ring with various groups markedly influenced the HMBP activity, the order of potency (bromine > chlorine > fluorine = none) closely matching the atomic volume of the substituted group. Moreover, changes in the substitution position of the bromine group also affected the anti-proliferative activity, the more potent activity being obtained with para-substitution of the phenyl ring. In conclusion, this structure-activity study led us to identify the new aromatic HMBP [(4-Bromo-phenyl)-hydroxy-phosphono-methyl]-phosphonic acid as a potent in vitro anti-proliferative molecule against tumor cell lines (IC50 value of 9.5 x 10(-5) M). Interestingly, this compound can be further easily esterified on its phosphonic acid functions according to our chemical method and, thus, represents a potential candidate for the development of new esterified HMBP with enhanced pharmacokinetics.
Oligonucleotides present a high therapeutic potential for a wide variety of diseases. However, their clinical development is limited by their degradation by nucleases and their poor blood circulation time. Depending on the administration mode and the cellular target, these macromolecules will have to cross the vascular endothelium, to diffuse through the extracellular matrix, to be transported through the cell membrane, and finally to reach the cytoplasm. To overcome these physiological barriers, many strategies have been developed. Here, we review different methods of DNA vectorization, discuss limitations and advantages of the various vectors, and provide new perspectives for future development.
Furfural has become one of the most promising building blocks directly derived from biomass. It can be transformed into numerous important biobased chemicals. Among them, furfuryl ethers such as furfuryl ethyl ether (FEE) and tetrahydrofurfuryl ethyl ether (THFEE) are considered to be attractive derivatives, notably as fuel components, due to their high stability and high octane numbers. Therefore, the production of furfuryl ethers from furfural via a hydrogenation route is an important academic and industrial challenge and requires the deployment of new catalytic processes under green and competitive reaction conditions. The existing processes are based on a two-step process combining hydrogenation and reaction with a strong Bronsted acid catalyst in batch conditions. For the first time, a continuous flow one-step process has been elaborated for the conversion of furfural directly into furfuryl ethers based on reductive etherification. The present work explores the catalytic performance in a continuous flow of commercial palladium catalysts supported on activated carbon for the catalytic reductive etherification of furfural with ethanol in the presence of trifluoroacetic acid. The chemical and engineering aspects, such as the mechanisms and reaction conditions, will be discussed.
The premise of this work is the modification of the properties of chitosan-based film for possible use in food packaging applications. The biofilm was prepared via thermal and mechanical treatment through blending polymers with chitosan using Polyvinyl Alcohol (PVA) and loading different types of chemical agents, i.e., citric acid (CA), succinic acid (SA), and tetraethoxysilane (TEOS). The modification was carried out under high-speed homogenization at elevated temperature to induce physical cross-linkage of chitosan polymer chains without a catalyst. The findings showed that PVA improved the chitosan films' Tensile strength (TS) and elongation at break (Eb). The presence of chemicals caused an increase in the film strength for all samples prepared, in which a 5% w/w of chemical in the optimum composition CS/PVA (75/25) provided the maximum strength, namely, 33.9 MPa, 44.0 MPa, and 41.9 MPa, for CA-5, SA-5, and TEOS-5, respectively. The chemical agents also increased the water contact angles for all tested films, indicating that they promoted hydrophobicity. The chemical structure analysis showed that, by incorporating three types of chemical agents into the CS/PVA blend films, no additional spectral bands were found, indicating that no covalent bonds were formed. The thermal properties showed enhancement in melting peak and degradation temperature of the blend films, compared to those without chemical agents at the optimum composition. The X-ray diffraction patterns exhibited that PVA led to an increasing crystallization tendency in the blend films. The morphological observation proved that no irregularities were detected in CS/PVA blend films, representing high compatibility with both polymers.
