Synthesis of Water-soluble,Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids

Dendrimers are macromolecules characterized by high controlled size, shape and architecture, presence of inner cavities able to accommodate small molecules and many peripheral functional groups to bind target entities. They are of eminent interest for biomedical applications, including gene transfection, tissue engineering, imaging, and drug delivery. The well-known pharmacological activities of ursolic and oleanolic acids are limited by their small water solubility, non-specific cell distribution, low bioavailability, poor pharmacokinetics, and their direct administration could result in the release of thrombi. To overcome such problems, in this paper we described their physical incorporation inside amino acids-modified polyester-based dendrimers which made them highly water-soluble. IR, NMR, zeta potential, mean size of particles, buffer capacity and drug release profiles of prepared materials were reported. The achieved water-soluble complexes harmonize a polycationic character and a buffer capacity which presuppose efficient cell penetration and increased residence time with a biodegradable cell respectful scaffold, thus appearing as a promising team of not toxic prodrugs for safe administration of ursolic and oleanolic acids.     

N,N,N-Tris(tert-butoxycarbonyl)-l-arginine: five isoforms whose obtainment depends on procedure and scrupulous NMR confirmation of their structures

Research on Chemical Intermediates - l-arginine is often covalently linked to vectors for gene or drug delivery as a means of increasing their transfection activity and reducing toxicity. This...     

Synthesis of crosslinked nanostructured saccharidic vinyl copolymers and their functionalization

Saccharidic monomers and a macromonomer were synthesized and copolymerized in the presence of divinylbenzene (DVB) as crosslinker in conditions of separation of phases to give hydrophilic nanostructured sugar-based vinyl copolymers. Appropriate model molecules such as N-benzyl-d-gluconamide for the saccharidic copolymers and 4-(4-chlorobutoxy)benzaldehyde and (E)-4-(4-chloro-2-butenyloxy)benzaldehyde for electrophilic reagents prefiguring possible copper amine oxidase inhibitors allowed identification of conditions for useful monofunctionalizations mainly at the position 2 of the saccharidic units. The examined samples of the nanostructured copolymers from one of the monomers proved to be stable enough to tolerate the functionalization reactions without loss of morphology.     

One-Step,Low-Cost,Operator-Friendly,and Scalable Procedure to Synthetize Highly Pure N-(4-ethoxyphenyl)-retinamide in Quantitative Yield without Purification Work-Up

It is widely reported that N-(4-hydroxyphenyl)-retinamide or fenretinide (4-HPR), which is a synthetic amide of all-trans-retinoic acid (ATRA), inhibits in vitro several types of tumors, including cancer cell lines resistant to ATRA, at 1–10 µM concentrations. Additionally, studies in rats and mice have confirmed the potent anticancer effects of 4-HPR, without evidencing hemolytic toxicity, thus demonstrating its suitability for the development of a new chemo-preventive agent. To this end, the accurate determination of 4-HPR levels in tissues is essential for its pre-clinical training, and for the correct determination of 4-HPR and its metabolites by chromatography, N-(4-ethoxyphenyl)-retinamide (4-EPR) has been suggested as an indispensable internal standard. Unfortunately, only a consultable old patent reports the synthesis of 4-EPR, starting from dangerous and high-cost reagents and using long and tedious purification procedures. To the best of our knowledge, no article existed so far describing the specific synthesis of 4-EPR. Only two vendors worldwide supply 4-ERP, and its characterization was incomplete. Here, a scalable, operator-friendly, and one-step procedure to synthetize highly pure 4-EPR without purification work-up and in quantitative yield is reported. Additionally, a complete characterization of 4-EPR using all possible analytical techniques has been provided.     

Soluble and insoluble polymeric 1,3-dithiane reagents for the synthesis of aldehydes from alkyl halides

Through the synthesis and study of model systems as proper dithiane derivatives, vinyl monomers and soluble copolymeric reagents containing 2-unsubstituted 1,3-dithiane rings, we attained the key synthon 1,3-dithiane-5-methanol. Through its reaction with commercial resins, new polymeric reagents useful for supported organic synthesis and combinatorial chemistry were developed. Exploiting the reactivity of position 2 in 1,3-dithiane rings, such polymeric reagents were employed in the production of aldehydes from alkyl halides through a process entirely free from unpleasant odors.     

Nanostructured styrenic co-polymers containing glucopyranosyl residues and their functionalization

Sugar-based co-polymers with saccharidic units in stable cyclic form and nanometric morphologies stabilized through crosslinking, adaptable through specific functionalizations to biochemical interaction studies with copper-containing amine oxidases, were synthesized from appropriate monomers and macromonomers. The most promising nanospherical co-polymer obtained, containing β-d-glucopyranosidic units, was employed in functionalization reactions with the help of model molecules, achieving useful transformations mainly at the 6-position and to a minor extent at the 2-position of the saccharidic system.     

Monomers containing substrate or inhibitor residues for copper amine oxidases and their hydrophilic beaded resins designed for enzyme interaction studies

Five styrenic monomers, four with aminoalkyl residues typical of copper containing amine oxidase substrates and one with a 2,6-dialkoxybenzylamine residue which mimics previously prepared selective substrate-like benzylamine oxidase inhibitors, have been synthesized and transformed into radical homopolymers, copolymers with N,N-dimethylacrylamide (DMAA), and hydrophilic beaded resins, designed for enzyme interaction studies aimed in finding new materials for highly biospecific chromatographic separations. The five monomers have given beaded resins of 125-500 μm swellable in water with a volume increase of 1200-1500%. The four aminoalkyl monomers have given water soluble copolymers some of which are good substrates of benzylamine oxidase (BAO), diamine oxidase (DAO) and lysyl oxidase (LO), up to 9.7 times better than elastin for LO.