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Julio Alvarez-Builla

Publications and source records attributed to Julio Alvarez-Builla.

11 recordsLinked to original sources
PubMed2004

Pyrrolodiazines. 6. Palladium-catalyzed arylation, heteroarylation, and amination of 3,4-dihydropyrrolo[1,2-a]pyrazines.

The palladium-catalyzed Suzuki cross-coupling reaction of arylboronic acids and 6-bromo- and 6,8-dibromo-3,4-dihydropyrrolo[1,2-a]pyrazines afforded 6-substituted and 6,8-disubstituted 3,4-dihydropyrrolo[1,2-a]pyrazines in good yields. Stille and Negishi coupling reactions have been used to prepare 6-heteroaryl-substituted derivatives in moderate yields by employing heteroaryl halides and 6-metalated 3,4-dihydropyrrolo[1,2-a]pyrazines as reaction partners. A variety of cyclic secondary amines have also been incorporated at position C-6 of 6-bromo-1-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine in the presence of the palladium catalyst Pd(2)(dba)(3) in conjunction with BINAP as ligand. This amination reaction is one of the few reported examples of such a palladium-catalyzed transformation on a pyrrole ring, although the reaction could not be extended to less nucleophilic amines.

Alkylation↗
PubMed2004

Sonogashira reaction on quinolizium cations.

The four isomeric bromoquinolizium bromides reacted with aryl- and heteroarylacetylenes under Sonogashira conditions. The reactions proceed with moderate-to-high yields to afford aryl- and heteroarylethynyl quinolizium cations. This is the first reported example of the Sonogashira reaction on heteroaromatic cations, and it allowed easy access to potential pi-donor pi-acceptor systems bearing cationic units.

Journal Article↗
PubMed2004

Reaction of bromomethylazoles and tosylmethyl isocyanide. A novel heterocyclization method for the synthesis of the core of marine alkaloids variolins and related azolopyrimidines.

A novel and efficient synthesis of the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine system, the heterocyclic core of the variolin family of marine alkaloids, is described. The route involves the reaction of 3-bromo-2-(bromomethyl)pyrrolo[2,3-b]pyridine and tosylmethyl isocyanide (TosMIC) under phase-transfer conditions. This unprecedented reaction was also used to synthesize a series of new methoxycarbonyl azolopyrimidines by reaction of TosMIC with bromomethylindoles, bromomethylbenzimidazole, and bromomethylpyrazole. Hydrolysis and decarboxylation of 5-bromo-7-methoxycarbonylpyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine obtained by this heterocyclization process and installation of the pyrimidine moiety in the C5 position open an alternative approach to complete a total synthesis of variolin B.

Alkaloids↗
PubMed2004

Benzo[f]azino[2,1-a]phthalazinium cations: novel DNA intercalating chromophores with antiproliferative activity.

New azaquinolizinium-type cations have been obtained from isochromane. The synthesis was completed over seven steps and included as the key feature an intramolecular Westphal condensation. This first example of the intramolecular process allowed the preparation of benzo[f]pyrido[2,1-a]phthalazinium and benzo[f]quino[2,1-a]phthalazinium salts, which were evaluated as DNA intercalators, DNA topoisomerase I inhibitors, and antiproliferative compounds. Both cationic systems behave as DNA intercalators and exhibit antiproliferative activity. The pentacyclic benzo[f]quino[2,1-a]phthalazinium cations also have an inhibitory effect on the catalytic activity of DNA topoisomerase I, without trapping of cleavage complexes. Structural characterization using density functional theory indicates that the fused ring systems are slightly nonplanar, and additional molecular modeling studies suggest a preferred orientation for the intercalating chromophores within a typical CpG or TpG intercalation site.

Antineoplastic Agents↗
PubMed2003

Westphal reaction in solid-phase.

[reaction: see text]. A library of cycloimonium salts has been prepared through Westphal reaction in solid-phase. By reaction of solid-support-bound azolium or azinium acetates 2, 1,2-diketones 4, and base, cycloimonium salts 5 were synthesized in good to high yield and purities.

Journal Article↗
PubMed1996

Pyrrolodiazines. 2. Structure and Chemistry of Pyrrolo[1,2-a]pyrazine and 1,3-Dipolar Cycloaddition of Its Azomethine Ylides.

A new synthesis of the pyrrolo[1,2-a]pyrazine system from pyrrole is described. In light of the ab initio calculations carried out on this heterocyclic system some of its basic chemistry was investigated and included electrophilic substitution, addition of organolithium reagents, metalation with lithium diisopropylamide and subsequent reaction with electrophiles, and formation of salts by quaternization of the nonbridgehead nitrogen. N-ylides obtained from these salts undergo 1,3-dipolar cycloaddition with suitable dipolarophiles to give dipyrrolo[1,2-a]pyrazines, pyrazolo[1,5-a]-pyrrolo[2,1-c]pyrazines, and heterobetaines. Examples of intramolecular 1,3-dipolar cycloadditions are also reported.

Journal Article↗