José Luis Díaz

Dihydropyridines in MCRs. Tandem processes leading to modular tetrahydroquinoline systems with up to 6 diversity elements.

An efficient, modular method for the synthesis of highly substituted tetrahydroquinoline systems is described. The Lewis acid catalyzed interaction of dihydropyridines with glyoxalate and anilines affords the heterocyclic parent systems in good yields. Tandem one-pot processes allow the incorporation of additional components: a preliminary nucleophilic attack on pyridinium salts generates the reactive dihydropyridine in situ, and subsequent electrophilic reactions on the secondary amine complete the assembly of the final targets, which have up to 6 diversity points.

A Unified Synthesis of Bifunctional 4‐Substituted‐1,2,3,4‐tetrahydroisoquinoline Derivatives

Abstract Starting from a single, commercially available bromoisoquinoline, convenient (multigram) syntheses of 4‐substituted‐1,2,3,4‐tetrahydroisoquinoline derivatives have been developed. The compounds thus prepared show suitable substitution patterns for further derivatization and constitute a new family of compounds of potential pharmacological interest.

Indoloquinolizidine–Peptide Hybrids as Multiple Agonists for D1 and D2 Dopamine Receptors

Multiple‐specificity ligands are considered promising pharmacological tools that may show higher efficacy in the treatment of diseases for which the modulation of a single target is therapeutically inadequate. We prepared a set of novel ligands for D1 and D2 dopamine receptors by combining two indolo[2,3‐a]quinolizidine scaffolds with various tripeptide moieties. The binding and functional properties of these molecules were determined by radioligand binding studies in brain striatum membranes and by intracellular cAMP production assays in cells expressing different dopamine receptor subtypes. Some indoloquinolizidine–peptide hybrids, mainly with the trans configuration, showed dual agonist activity at both D1 and D2 dopamine receptors and may therefore be useful for testing the therapeutic potential of multivalent drugs on these targets.

Synthesis of polyconjugated carbazolyl–oxazolones by a tandem hydrozirconation–Erlenmeyer reaction. Study of their hyperpolarizability values

Abstract New push–pull systems with carbazole as donor moiety and oxazolone as electron withdrawing group have been synthesized by an AgClO 4 -catalyzed hydrozirconation and ulterior Erlenmeyer reaction. Studies carried out with the semiempirical quantum method PM3 (MOPAC93) pointed a low dependence of the hyperpolarizability value on the number of double bonds at the conjugated bridge by β (0)∝ n 0.8 . Introduction of rigidity in the polyene chain or additional donor groups in the carbazole moiety pointed to exertion of a large effect on hyperpolarizability values that could avoid unnecessary efforts in costly path elongation synthesis.

Fast and Efficient Access to a Family of Multifunctional 1,3,5-Trisubstituted Piperidines

Abstract A collection of new 1,3,5-trisubstituted piperidines has been synthesized starting from the commercially available 5-bromonicotinic acid. A unified, diastereoselective strategy allows the controlled access to both cis and trans stereochemistries. The heterocyclic compounds thus prepared bear multiple functional groups suitable for structural diversification and combichem protocols.

Productive trapping of NAD-type radicals. Non-biomimetic reduction of pyridinium saltsElectronic supplementary information (ESI) available: experimental procedure and characterization data. See: http://www.rsc.org/suppdata/cc/b2/b201813f/

One-electron reduction of pyridinium salts (NAD+ analogues) generates dihydropyridyl radicals which may then be engaged in radical addition processes to regioselectively form gamma-substituted dihydropyridines.