Antonino Corsaro

Chemical Synthesis of Heterocyclic−Sugar Nucleoside Analogues

Dipartimento Farmaco-Chimico, Università di Messina, Via SS Annunziata, 98168 Messina, Italy, Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy, and Laboratorio de Sintesis Asimetrica, Departamento de Quimica Organica, Instituto de Ciencia de Materiales de Aragon, Universidad de Zaragoza, CSIC, E-50009 Zaragoza, Aragon, Spain, Pedro Merino: pmerino@unizar.es

Recent advances in small organic molecules as DNA intercalating agents: Synthesis, activity, and modeling

The interaction of small molecules with DNA plays an essential role in many biological processes. As DNA is often the target for majority of anticancer and antibiotic drugs, study about the interaction of drug and DNA has a key role in pharmacology. Moreover, understanding the interactions of small molecules with DNA is of prime significance in the rational design of more powerful and selective anticancer agents. Two of the most important and promising targets in cancer chemotherapy include DNA alkylating agents and DNA intercalators. For these last the DNA recognition is a critical step in their anti-tumor action and the intercalation is not only one kind of the interactions in DNA recognition but also a pivotal step of several clinically used anti-tumor drugs such as anthracyclines, acridines and anthraquinones. To push clinical cancer therapy, the discovery of new DNA intercalators has been considered a practical approach and a number of intercalators have been recently reported. The intercalative binding properties of such molecules can also be harnessed as diagnostic probes for DNA structure in addition to DNA-directed therapeutics. Moreover, the problem of intercalation site formation in the undistorted B-DNA of different length and sequence is matter of tremendous importance in molecular modeling studies and, nowadays, three models of DNA intercalation targets have been proposed that account for the binding features of intercalators. Finally, despite DNA being an important target for several drugs, most of the docking programs are validated only for proteins and their ligands. Therefore, a default protocol to identify DNA binding modes which uses a modified canonical DNA as receptor is needed.

Selectivity in cycloadditions-IX: Cycloadditions of nitrile oxides to indoles. Reactivity and regiochemistry

Abstract Cycloadditions of benzonitrile oxide and mesitonitrile oxide to N-methylindole and indole yield the acid sensitive cycloadducts 1 a-d with high regioselectivity. With N-carbethoxyindole the stable cycloadducts 1 e,f and minor amounts of the regioisomeric 2 e,f are isolated. The electron withdrawing substituent reduces both the regioselectivity and the reactivity of the cycloadditions. Frontier orbital considerations, based on MINDO/3 calculations, allow elucidation of the observed changes in reactivity and regiochemistry.

Isoxazolidine analogues of pseudouridine: a new class of modified nucleosides

Abstract A new class of modified C-nucleosides has been synthesized according to the 1,3-dipolar cycloaddition methodology. The obtained compounds are structurally related to natural pseudouridine, where the sugar moiety is replaced by an isoxazolidine ring. Different experimental conditions, and the effect of additives on the cycloaddition process, have been examined; the best results were obtained when the cycloaddition reaction was performed under microwave irradiation

C-Alkoxycarbonyl Nitrones: Building Blocks for the Synthesis of Butenolides, Lactams and Modified Nucleosides

Abstract: Elaboration of isoxazolidines derived from the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to suitably substituted alkenes leads to the development of new synthetic methodologies for the preparation of a wide range of natural products and derivatives including lactones, lactams and complex nucleosides. The insertion of a chiral centre in position α, with respect to nitrone functionality, or the presence of a chiral auxiliary at the nitrogen atom have allowed the enantioselective synthesis of the same compounds.

Diastereo- and enantioselective synthesis of N,O-nucleosides

Abstract The diastereo- and enantioselective synthesis of α- and β-3′-hydroxymethyl-N,O-nucleosides is described, based on the 1,3-dipolar cycloaddition of a N-glycosyl nitrone. Two approaches have been evaluated: the one-step procedure, which uses vinyl nucleobases, showed a better stereoselectivity towards β-nucleosides.

Stereoselective synthesis of homochiral annulated sultams via intramolecular cycloaddition reactions

Abstract Different homochiral dipoles containing a sulfonamido group have been synthesized, starting from l -amino acids, and used for the construction of functionalized and enantiomerically pure annulated sultams.

α-Amino acids as chiral educts for stereoselective syntheses of pyrrolidine and pyrrolizidine systems☆

Abstract Homochiral functionalized pyrrolidine and pyrrolizidine systems have been achieved by stereoselective intramolecular 1,3-dipolar cycloaddition of homochiral nitrones, starting from homochiral amino acids, and by subsequent reduction of the obtained cycloadducts.

An asymmetric approach to pyrrolidinone and pyrrolizidinone systems by intramolecular oxime-olefin cycloaddition

Abstract Homochiral functionalized pyrrolidinone and pyrrolizidinone systems have been achieved by stereoselective intramolecular oxime-olefin cycloaddition starting from homochiral amino acids, and by subsequent reduction of the obtained fused isoxazolidines.

A Stereoselective Approach to Isoxazolidinyl Nucleosides

A stereoselective approach towards isoxazolidinyl nucleosides has been designed. The 1,3-dipolar cycloaddition of a C-chiral nitrone with purine and pyrimidine nucleobases produces thymidine and adenine N,O-nucleosides, in enantiomerically pure forms.