Regioselective halogenation of aminopyrimidinyl-pyrrole carboxylic acid derivatives

The regioselective synthesis of halogenated aminopyrimidinyl-pyrroles as useful scaffolds for the preparation of diversified selective kinase inhibitors is described. The chemistry is simple and mostly based on the use of N-halosuccinimides under mild reaction conditions but the regioselectivity observed is partially unexpected.     

Regiospecific total synthesis of 6-deoxyanthracyclines

Regiospecific approaches to 6-deoxyanthracyclinones, which have resulted in the synthesis of the novel anthracyclines 4-demethoxy-6-deoxydaunorubicin (2) and 6-deoxycarminomycin (3), are reported. The construction of the aglycone 4 is based on the coupling of l,4-dimethoxy-2-lithionaphthalene (10) to 1 formyl-2-carbomethoxy-4-acetylcyclohexane thioketal (11). A new improved regioselective route, which allows the preparation of 6-deoxyanthracyclinones bearing also substituents in ring Das illustrated by 5, 'a based on the coupling of 10a and of l,4,5-trimethoxy-3-lithionaphthalene (10b) to lactone 28.     

Highly efficient synthesis of 5-benzyl-3-aminoindazoles

A rapid and efficient procedure for the preparation of 5-benzyl-3-aminoindazoles 1 is reported. Key intermediates are fluoro-cyano diarylmethanes 2 which have been obtained by two different synthetic approaches. Benefits of these methods result from the use of commercially available starting materials and practical experimental conditions that allow easy scale-up.     

Synthesis of novel derivatives of 1H-imidazo[1,2-b]pyrazole as potential CNS-agents

As part of a preliminary study on novel 5-HT₃ ligands, the synthesis of a series of 1H-imidazo[1,2-b]-pyrazole derivatives is described. The bicyclic heteroaromatic nucleus was functionalized at positions 1, 6 and 7 to give the series of tropanyl derivatives 4a-g, 12a, 12d (Table 1). Different synthetic approaches were utilized to obtain the desired molecules: endo and exo 6-amides 4a, 12a and 6-ester 4b required two independent schemes due to the opposite behavior of the intermediate imidazolide 3 towards tropine and tropanamine. The 7-congeners, ester 4c , its tropinium salt 4e , the endo and exo amides 4d and 12d were prepared from the known common precursor 8 [1], while derivatives 4f-g , originated by functionalizing position 1, were obtained from 1H-imidazo[1,2-b]pyrazole by direct N-acylation. Since the structural features of these molecules seemed to meet the main rules of the S.A.R. studies published so far [2-5], they were evaluated “in vitro” for 5-HT₃ receptor affinity (Table 2). The biochemical data show significant activity for derivatives 4a-e, 4g. These results are encouraging and justify further investigational work on this class of molecules.     

Anthracyclines and related substances. 4. A novel regio- and stereoselective total synthesis of 7-epidaunomycinone and daunomycinone.

Daunomycinone $\text{2a}$ has been synthesized by a novel regio- and stereoselective route that establishes the tetracyclic framework and the C-7 oxygen in naphthacenol $\text{5c}$ via a double Friedel-Crafts acylation.     

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.     

Flexible synthetic route to 6-deoxy and 11-deoxyanthracyclinones

The regiospecific synthesis of 6-deoxydaunomycinone 3 and 1-hydroxy-4-demethoxy-11-deoxydaunomycinone (4) is reported: the route allows the preparation of 6-deoxy or 11-deoxyanthracyclinones through the γ or δ lactones 6 and 11.