Vittorio Pinciroli

Pyrrolo[3,2-c]quinoline derivatives: A new class of kynurenine-3-hydroxylase inhibitors

A series of pyrrolo[3,2-c]quinoline derivatives were synthesised and evaluated as inhibitors of selected enzymes of the kynurenine pathway. 7-Chloro-3-methyl-1H-pyrrolo[3,2-c]quinoline-4-carboxylic acid (7a) was found to be a relatively potent and selective inhibitor of kynurenine-3-hydroxylase (KYN-3-OHase). A molecular modelling study showed a good superimposition of 7a with PNU-156561 and kynurenine the natural substrate of KYN-3-OHase.

New rearranged products from the methylation of 13-oxobaccatin III

Treatment of 7-triethylsilyl-13-oxobaccatin III (1) with sodium hydride and methyl iodide gave the methylated ten-membered ring compound 2 that rearranged, via intramolecular aldol condensation, to unsaturated decalin ring system (3, 4, 5). These molecules were characterized by 1D and 2D NMR tecniques.

Preparation of novel 3,7-, 7,9- and 1,7-disubstituted guanines

Abstract Treatment of guanosine with arylmethyl halides in N,N-dimethylacetamide results in a series of 3,7-bis(arylmethyl) guanines and 7,9-bis(arylmethyl)guaninium halides. The same reaction on 7-arylmethyl guanines yields 3,7- and 7,9- differently disubstituted guanines. When 7-arylmethyl guanines are reacted with (hetero)arylmethyl halides in the presence of sodium hydride in N,N-dimethylformamide, 3,7- and 1,7-disubstituted guanines are obtained. All of these compounds, but one, are new and the preparation of 3,7-bis(substituted) guanines from guanosine as well as of 3,7- and 1,7-di(hetero)arylmethyl guanines from 7-substituted guanine is unprecedented.

Nucleophilic substitution on α-mesyloxy-O-alkyloximes—II. Enantiospecific synthesis of 2-(imidazol-1-yl)-1-cyclohexyl-3-phenylpropan-1-one O-alkyloximes

Abstract An enantiospecific synthesis of (S)- and (R)-(E)-5-[1-cyclohexyl-3-phenyl-2-(imidazol-1-yl)propylidene]aminooxypentanoic acids 2 using homochiral phenylalanines as starting material is described. Protected α-hydroxy-N,O-dimethylamides 4 , obtained from α-hydroxyacids 3 were coupled with 1-cyclohexenyllithium to afford α,β-enones 5 , which were in turn converted to α-hydroxyketones 6 . Configurational liability of compound 11 , prompted us to attempt imidazole introduction on the α-hydroxy-O-alkyloxymes 12 which proved to be configurationally more stable. Thus nucleophilic substitution on α-mesyloxy-O-alkyloxymes 14 led, after ester removal, to homochiral compounds 2 . The use of hydrogenolysis for 14b deblocking provided 2a with 97% ee. Considerations on the stereochemical outcome of this hitherto undescribed nucleophilic substitution on α-mesyloxy-O-alkyloxymes are reported.

NEW 13-AZA BACCATINS

Abstract Upon treatment of 7-triethylsilyl-10, 13-dideoxy-13-imino baccatin III (2) subsequently with diazomethane and m-chloroperbenzoic acid a few novel derivatives, namely methylimine 3 and oximes 4 and 5, were obtained. Interestingly, 4 is characterized by the hydroxyl at position 14.