Antonio Dore

Novel atropisomeric phosphorus ligands: 4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine derivatives

Abstract Atropisomerically pure (S)-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine 2b has been obtained by resolution of the racemic compound with an enantiopure palladium complex and its absolute configuration has been determined by X-ray analysis; it is an effective chiral ligand for the asymmetric hydroformylation of styrene with rhodium catalysts.

New axially chiral sulfur compounds: Synthesis and conformational stability of enantiopure 4,4′-biphenanthrene-3,3′-dithiol and related atropisomeric derivatives

Abstract Enantiopure (R)- and (S)-4,4′-biphenanthrene-3,3′-dithiol 1a has been prepared for the first time through a synthetic procedure involving in the key step a stereoconservative Newman-K wart thermorearrangement of the bis -N,N-dimethylthiocarbamoyl ester of (R)- and (S)-biphenanthrol 2b , respectively. The atropisomeric conformations of 1a are not interconverted even at temperatures as high as 285° C. whereas the related biphenanthrothiophene 3 is completely racemized in a few minutes at 250° C. The axially chiral backbone of 1a has been incorporated in a set of novel C 2 symmetry sulfur reagents suitable for a variety of stereoselective reactions.

Synthesis and SAR study of novel tricyclic pyrazoles as potent phosphodiesterase 10A inhibitors.

Novel pyrazolo[5,1-f][1,6]naphthyridines, pyrazolo[5,1-a][2,6]naphthyridines, pyrazolo[5,1-a][2,7]naphthyridines and pyrazolo[5,1-a]isoquinolines phenylimidazole/benzimidazole ethylene-linked were designed and synthesized for PDE10A interaction. An AgOTf and proline-cocatalyzed multicomponent methodology based on use of o-alkynylaldehydes, tosylhydrazide and ketones was developed and proved to be a convenient route for assembly of most of the novel tricyclic pyrazoles synthesized. Pyrazolo[5,1-f][1,6]naphthyridine 43 and 59, pyrazolo[5,1-a][2,6]naphthyridine 66, and pyrazolo[5,1-a][2,7]naphthyridine 42 showed the highest affinity for PDE10A enzyme (IC50 = 40, 42, 40, 55 nM, respectively).

Dinaphtho[2,1-b; 1′,2′-d]phospholes: a new class of atropisomeric phosphorus ligands

The parent and some alkyl and aryl substituted dinaphtho[2,1-b; 1′,2′-d]phospholes 1 have been synthesized and shown to be atropisomerically stable below room temperature.

Synthesis, molecular modeling and SAR study of novel pyrazolo[5,1-f][1,6]naphthyridines as CB2 receptor antagonists/inverse agonists.

Pyrazolo[5,1-f][1,6]naphthyridine-carboxamide derivatives were synthesized and evaluated for the affinity at CB1 and CB2 receptors. Based on the AgOTf and proline-cocatalyzed multicomponent methodology, the ethyl 5-(p-tolyl)pyrazolo[5,1-f][1,6]naphthyridine-2-carboxylate (12) and ethyl 5-(2,4-dichlorophenyl)pyrazolo[5,1-f][1,6]naphthyridine-2-carboxylate (13) intermediates were synthesized from the appropriate o-alkynylaldehydes, p-toluenesulfonyl hydrazide and ethyl pyruvate. Most of the novel compounds feature a p-tolyl (8a-i) or a 2,4-dichlorophenyl (8j) motif at the C5-position of the tricyclic pyrazolo[5,1-f][1,6]naphthyridine scaffold. Structural variation on the carboxamide moiety at the C2-position includes basic monocyclic, terpenoid and adamantine-based amines. Among these derivatives, compound 8h (N-adamant-1-yl-5-(p-tolyl)pyrazolo[5,1-f][1,6]naphthyridine-2-carboxamide) exhibited the highest CB2 receptor affinity (Ki=33nM) and a high degree of selectivity (KiCB1/KiCB2=173:1), whereas a similar trend in the near nM range was seen for the bornyl analogue (compound 8f, Ki=53nM) and the myrtanyl derivative 8j (Ki=67nM). Effects of 8h, 8f and 8j on forskolin-stimulated cAMP levels were determined, showing antagonist/inverse agonist properties for such compounds. Docking studies conducted for these derivatives and the reference antagonist/inverse agonist compound 4 (SR144528) disclosed the specific pattern of interactions probably related to the pyrazolo[5,1-f][1,6]naphthyridine scaffold as CB2 inverse agonists.

Generation and rearrangement of C2-symmetric chiral allyl anions derived from dibenzo- and 1,1'-dinaphtho-2,2-'dithiopropenes

Abstract The allyl anions generated from 4 H -dinaphtho[2,1- f :1′,2′- h ][1,5]dithionin ( 6 ) and 2-ethenyl-dinaphtho[2,1- d :1′,2′- f ][1, ( 8 ) rearranged both to the thiolate 10 which further reacted with water or methyl iodide to afford 9 or 12 respectively. A similar behavior was exhibited by the anion of 4 H -dibenzo[ f,h ][1,5]dithionin ( 15 ).

4H-dinaphtho[2,1-f:1′,2′-h][1,5]dithionin-S,S′-tetroxide: Preparation, structure elucidation and facile intramolecular [2+2]-photocyclization

Abstract The preparation of compound 1, a conformational study in solution and the unexpectedly facile rearrangement into 2 via photochemical intramolecular [2+2]-cycloaddition is described: the structure of these compounds have been investigated by NMR and X-ray diffraction.