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This work shows the synthesis of a drug delivery system made of casein nanoparticles able to host hydrophobic molecules and be functionalized with aptamers targeting the epidermal growth factor receptor.

Hybrid hydrogels made of chemically modified pectin, gelatin and xanthan gum have been formulated and processed through a double crosslinking step, aimed at wound healing applications. The formulation of hybrid hydrogels finds its cornerstone in the possibility to create a supportive environment for cell adhesion and proliferation, ensuring the transport of nutrients via porous structures, together with mechanical properties closely comparable to the native tissue. The hydrogels present a good swelling behavior, resistance to dissolution and fragmentation in simulated biological environment (PBS 1× and DMEM) for up to 20 days and the porous structure, as pictured via scanning electron microscopy, has been foreseen to help cell migration and the exchange of biomolecules. Rheological characterization showed desired mechanical features, while the biocompatibility has been assessed via live/dead assay on murine fibroblasts. Finally, the hybrid hydrogels have also been proved suitable for mechanical extrusion, demonstrating the possibility of cell encapsulation in the future perspective of 3D bioprinting applications.

The first one-step synthesis of dumbbell-like gold–iron oxide nanoparticles has been reported here. Surface functionalization with a biocompatible chitosan matrix allowed us to obtain a novel targetable diagnostic and therapeutic tool.

The catalytic asymmetric inverse-electron-demand (IED) [4+2] cycloaddition of various salicylaldehyde-derived N-arylimines with electron-rich alkenes in the presence of chiral BINOL-derived phosphoric acid catalysts has been studied with the aim of obtaining optically active 4-aminobenzopyran derivatives. Dienophiles such as 2,3-dihydro-2H-furan, benzyl N-vinylcarbamate and 2-vinylindole have been employed.

1,3-Dipolar cycloaddition of C-aryl-N-aryl- and C-carboxymethyl-N-aryl-nitrile imines with functionalized acetylenes have been studied. Regioisomeric mixtures have been obtained with the 5-substituted pyrazole as the major cycloadduct. Under scandium triflate catalysis a reversal in the regiochemistry was observed, especially in the case of C-carboxymethyl-N-aryl-nitrile imines.

Indoles bearing Michael acceptors at the 4-position were engaged in organocatalytic enantioselective cascade reactions with enals. Careful optimisation of the reaction parameters overcame the inherent low reactivity of these substrates, rendering 3,4-ring fused indoles in good yields, excellent enantioselectivities and as single diastereoisomers.

Some N-Boc ynamides bearing a terminal ester or aryl group are treated with azides to produce the desired triazoles with complete regiocontrol.

The synthesis of levetiracetam and its enantiomer by deracemization of (±)-2-bromobutyric acid using either ( S )- or ( R )- N -phenylpantolactam as chiral auxiliaries, followed by S N 2 substitution of the bromine atom by a 2-oxopyrrolidin-1-yl group and amidation of the carboxylic acid, is described.

Enantiomerically pure central and planar chiral ferrocenyl cyanohydrins have been used for the synthesis of previously unreported 5-ferrocenyl-oxazolines and a 5-ferrocenyl-thiazoline where the central chirality lies on the carbon bearing the oxygen or the sulfur atom. The epimerization at C 5 of the oxazoline ring has also been investigated.

Enantiopure fluorinated isoxazolidines and amino polyols were obtained from the 1,3-dipolar cycloaddition of allylic fluorides and Z-α-phenyl-N-methylnitrone under environment-friendly conditions.

A synthesis of ferrocenyl-oxazolines is described using an iodide-mediated ring expansion of N-ferrocenoyl-aziridine-2-carboxylic esters. The ring enlargements take place with full stereocontrol, namely net retention of configuration. Modification of the ester function by a Grignard reaction leads to three new types of ferrocenyl-oxazoline carbinol ligands, which were used as chiral ligands in the asymmetric addition of diethylzinc to benzaldehyde (e.e.s ranging from 46 to 62%). The planar chiral ferrocenyl-oxazoline carbinol ligand gave a very good result (e.e. 90%) in the palladium-catalyzed allylic substitution of 1,3-diphenyl prop-2-enylacetate with dimethyl malonate.

A new protocol is described for the stereocontrolled synthesis of pseudo-C(2)-symmetric core units of interest as candidates for HIV protease inhibition. Addition of unbranched and branched organolithium reagents to cyanohydrins from l-phenylalaninal and l-isoleucinal, followed by in situ reduction of the intermediate imines and CHT deprotection under MW irradiation, led to 1,3-diamino alcohols 6a and 8a as the major products in satisfactory to good yields. The first preparation of a previously unreported pseudo-C(2)-symmetric triamino derivative was accomplished expeditiously via high-yielding nitro-Mannich addition of the silylnitronate, from 2-phenyl-1-nitroethane, to the PMP imine derived from l-phenylalaninal. Reduction of the nitro group in the moderately unstable nitro diamine adduct, followed by chromatographic separation of the required diastereoisomer and CHT debenzylation under MW irradiation, led to the 2-PMP-protected triamine 19 isolated as a bis(sulfonamide).

The 5-amino-1,2,3-triazole-4-carboxylic acid is a suitable molecule for the preparation of collections of peptidomimetics or biologically active compounds based on the triazole scaffold. However, its chemistry may be influenced by the possibility of undergoing the Dimroth rearrangement. To overcome this problem, a protocol based on the ruthenium-catalyzed cycloaddition of N-Boc ynamides with azides has been developed to give a protected version of this triazole amino acid. When aryl or alkyl azides are reacted with N-Boc-aminopropiolates or arylynamides, the cycloaddition occurs with complete regiocontrol, while N-Boc-alkyl ynamides yield a mixture of regioisomers. The prepared amino acids were employed for the preparation of triazole-containing dipeptides having the structural motives typical of turn inducers. In addition, triazoles active as HSP90 inhibitors (as compound 41, IC50 = 29 nM) were synthesized.

The allylation of acylsilanes with tetraallyltin in the presence of catalytic amounts of Sc(OTf) 3 proceeded smoothly to afford the silylated homoallylic alcohols in good yields. Subsequent protiodesilylation gave the formal adducts of the corresponding aldehydes. The homochiral acylsilane 11 gave a reversal of asymmetric induction in the Sc(OTf) 3 catalyzed allylation and in the Sakurai reaction.

A detailed investigation of the desilylation of (Z)-α-dimethylphenylsilyl vinyl sulfides with fluoride ion has shown that in substrates containing an electron-withdrawing group β to the sulfur, phenyl group migration occurs as a result of a fluoride ion catalyzed retro-Michael reaction.

Several small organic molecule catalysts are reminiscent of natural enzymes in their mode of action and substrate interaction/activation. This striking similarity has been a great source of inspiration for the development of new organocatalytic asymmetric processes. A few representative examples, mostly dealing with catalysts interacting through multiple hydrogen-bonds (synthetic oxyanion holes), are highlighted in this perspective.

It is demonstrated, that the stereochemical outcome of Wittig olefinations of 4-substituted cyclohexanones can be controlled by hydrogen-bond donor catalysts such as (R,R)-TADDOL or 1,2-diaminocyclohexane derived bis-thioureas.

Several small organic molecule catalysts are reminiscent of natural enzymes in their mode of action and substrate interaction/activation. This striking similarity has been a great source of inspiration for the development of new organocatalytic asymmetric processes. A few representative examples, mostly dealing with catalysts interacting through multiple hydrogen-bonds (synthetic oxyanion holes), are highlighted in this perspective.

Click chemistry based on a 1,3-dipolar cycloaddition between lipophilic gold nanorods (GNRs) containing an acetylene group with spherical silver nanoparticles containing an azide has been accomplished (see scheme). Phantom experiments show that this organic transformation did not affect the suitability of the gold nanorods as contrast agents for optoacoustic imaging.

Aldimines (II) or (V) and dihydrofuran (III) or vinylindole (XII) give exclusively the desired enantioenriched aminobenzopyrans.

The allylation of acylsilanes with tetraallyltin in the presence of catalytic amounts of Sc(OTf) 3 proceeded smoothly to afford the silylated homoallylic alcohols in good yields. Subsequent protiodesilylation gave the formal adducts of the corresponding aldehydes. The homochiral acylsilane 11 gave a reversal of asymmetric induction in the Sc(OTf) 3 catalyzed allylation and in the Sakurai reaction.

1,3-Dipolar cycloaddition of C-aryl-N-aryl- and C-carboxymethyl-N-aryl-nitrile imines with functionalized acetylenes have been studied. Regioisomeric mixtures have been obtained with the 5-substituted pyrazole as the major cycloadduct. Under scandium triflate catalysis a reversal in the regiochemistry was observed, especially in the case of C-carboxymethyl-N-aryl-nitrile imines.

The new allylaminosilanes 2a – c , derived from chiral amines, react with benzaldehyde and pivalaldehyde in the presence of SnCl 4 to give homoallylic alcohols 4a – b with enantiomeric excesses of up to 30%.

A nitrogen-containing superbase such as TMG was found to be an effective catalyst for the reaction between N-diphenylphosphinoyl imines and nitroalkanes. Exploiting a protocol that avoids the use of any solvent also during workup procedure, we synthesized a series of beta-nitroamines in excellent yields and high diastereomeric ratios. These results, combined with the capability of the indium in conjunction with Zn as the stoichiometric reducing agent to perform in aqueous medium reduction of the nitro group under mild reaction conditions, led us to devise a three-step, one-pot synthesis of a range of 1,2-diamines, making use of environmentally friendly procedures in the various steps.

A series of new chiral oxazoline-1,3-dithianes has been easily synthesized and used as ligands for asymmetric catalysis. The conjugate addition of Et 2 Zn to enones resulted in ees of up to 69%, whereas the Pd-catalyzed allylic alkylation led to the expected products in almost quantitative yields and up to 90% enantioselectivity. The ligand’s conformation has been explored using a combination of X-ray and NMR measurements, indicating the presence of a remarkable anomeric effect, which accounts for the preference of the oxazoline ring for the axial location.

A novel double phase transfer process was achieved to develop PEG-based targetable nanostructures containing gold nanorods: in the first phase transfer, lipophilic free-CTAB gold nanorods have been obtained, by a straightforward one-step ligand exchange reaction in hydro-alcoholic mixture with thiols, then a second phase transfer was performed to entrap them into PEG-based polymeric nanoparticles.

The Rh complex catalysed hydrogenation of an α-(hydroxyalkyl)- N-methoxyacrylamide and the Ru complex catalysed hydrogenation of an α-(fluoroalkyl)acrylate both proceed with ≥90% selectivity to give the syn-isomer.

Treatment of methyl 1-methylsulfanylvinyl sulfoxides with sodium thiophenolate in MeOH gives 1-methylsulfanylalk-1-en-3-ols.

Enantiomerically pure β-hydroxyalkyl and β-aminoalkyl ferrocenyl sulfides have been synthesized in good yields from mercaptoferrocene and amino alcohol derivatives. Primary β-aminoalkyl sulfides allowed the synthesis of tetrahydro-1,4-thiazepines containing the ferrocene moiety with good diastereoselectivity and β-iminoalkyl sulfides. Some of these derivatives have successfully been employed as ligands for palladium-catalyzed allylic substitution, with asymmetric induction of up to 99% ee. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).