Mauro F. A. Adamo

Practical routes to diacetylenic ketones and their application for the preparation of alkynyl substituted pyridines, pyrimidines and pyrazoles

Alkynyl substituted pyridines, pyrimidines and pyrazoles have been synthesised by cyclocondensations of diacetylenic ketones with enamines, amidines and hydrazines, respectively.

The reactivity of 3-methyl-4-nitro-5-styrylisoxazole with some bis-enolisable ketones

The expected Michael adducts and spiroisoxazolines are obtained from the reaction between 3-methyl-4-nitro-5-styrylisoxazole and bis-enolisable ketones. Contrary to reported data, Michael adducts are obtained in good yields only when a substoichiometric amount of base is used, whereas spiroisoxazolines were obtained as the major product when the base is present in a large excess.

Catalytic Enantioselective Addition of Sodium Bisulfite to Chalcones

Dr. F. Fini, M. Scagnetti, Prof. M. F. A. AdamoCentre for Synthesis and Chemical Biology (CSCB)Department of Pharmaceutical and Medicinal ChemistryRoyal College of Surgeons in Ireland123 St. Stephen’s Green, Dublin 2 (Ireland)Fax: ( +353)1-402-2168E-mail: madamo@rcsi.ieHomepage: https://research1.rcsi.ie/pi/madamo/[

An improved synthesis of 3 -methyl -4 -nitro -5 -heteroarylethenylisoxazoles

A high yielding synthesis of polyfunctional scaffold 3-methyl-4-nitro-5-heteroarylethenylisoxazole is described. The novel condition allowed the preparation of reactive title compounds in high yield.

Synthesis of Homochiral Dihydroxy-4-nitroisoxazolines via One-Pot Asymmetric Dihydroxylation−Reduction

Herein we report a one-pot procedure to prepare a family of homochiral dihydroxy-4-nitroisoxazolines 3. This new methodology affords the title compounds in good yields, excellent enantiopurity, and without the use of chromatography.

An Improved Resolution Of 2-Methyl Piperidine And Its Use in The Synthesis Of Homochiral Trans-2,6-Dialkyl Piperidines

Abstract An efficient procedure for the resolution of 2-methylpiperidine is described. The enantiomers were used for a short and effective synthesis of the C2 symmetric piperidine, (+)-lupetidine and (+)-epidihydropinidine.

Design, synthesis and evaluation of aspirin analogues having an additional carboxylate substituent for antithrombotic activity.

Acetylsalicylic acid (aspirin) is an effective long-term prophylaxis of thrombotic events such as heart attacks and strokes. It covalently inhibits prostaglandin-H-synthase by interacting with Arg120 or Tyr385 at the active site allowing delivery of its acetyl group to Ser530. However the structure has not been optimized to fit the active site. We have designed acetylsalicylate analogues with an additional carboxylate substituent which allows simultaneous interaction with Arg120 and Tyr385 whilst positioning the acetyl group in close proximity to Ser530. One of these, an ester derivative which unlike acetylsalicylic acid is non-acidic, may act as useful lead compound for further exploitation of this approach.

Synthesis, structural and conformational properties, and gas phase reactivity of 1,4-dihydropyridine ester and ketone derivatives

A new series of 4-aryl-2,6-dimethyl-1,4-dihydropyridines, characterized by ester or ketone functions at positions 3 and 5, has been synthesized. Structural and conformational properties, concerning the dihydropyridine ring and the orientation (synplanar/antiperiplanar) of the substituents have been investigated in their crystal structure and in solution by nuclear magnetic resonance. Evaluation of intermolecular and hydrogen bonding interactions as well as packing features, have been also carried out, evidencing interesting packing motifs. Their gas phase reactivity, as protonated and deprotonated molecules, has been investigated by electrospray ionization, high resolution and collision-induced dissociation multiple stage mass spectrometry. Deydrogenation reactions have been observed as a function of the capillary voltage.

New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility

Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10-3 and 3 × 10-8 M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (< 0.20) was found in both formulations. Formulation 1 was selected to test in vitro drug release because it was superior in terms of encapsulation efficiency (62 %) and loading capacity (32 %). The solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile.

Desulfurative Chlorination of Alkyl Phenyl Sulfides

The chlorination of readily available secondary and tertiary alkyl phenyl sulfides using (dichloroiodo)benzene (PhICl2) is reported. This mild and rapid nucleophilic chlorination is extended to sulfa-Michael derived sulfides, affording elimination-sensitive β-chloro carbonyl and nitro compounds in good yields. The chlorination of enantioenriched benzylic sulfides to the corresponding inverted chlorides proceeds with high stereospecificity, thus providing a formal entry into enantioenriched chloro-Michael adducts. A mechanism implying the formation of a dichloro-λ4-sulfurane intermediate is proposed.