title: The utility of furan-, pyrrole-, and thiophene-based 2-silyloxy dienes as demonstrated by modular synthesis of annonaceous acetogenin core units and their pyrrolidine and thiolane analogues.
abstract: We report a modular strategy for obtaining the core units of annonaceous acetogenins and their nitrogen and sulfur analogues, which generates great structural diversity. This synthesis is based on the application of a reiterative vinylogous addition protocol involving a unique triad of silyloxy diene modules, 2-[(tert-butyldimethylsilyl)oxy]furan (TBSOF), N-(tert-butoxycarbonyl)-2-[(tert-butyldimethylsilyl)oxy]pyrrole (TBSOP), and 2-[(tert-butyldimethylsilyl)oxy]thiophene (TBSOT) and suitable heteroatom-stabilized carbenium ions. By combining TBSOF, TBSOP, and TBSOT nucleophilic synthons with certain tetrahydrofuran, pyrrolidine, and thiolane acceptors, the construction of varied, adjacently linked oligo-heterocyclic motifs related to the core segments of the annonaceous acetogenins is assured. At first, the reliability of the pivotal coupling maneuver was certified, by assembling a collection of 18 model constructs, covering all oxygen, nitrogen, and sulfur heteroatom combinations (i.e., compounds 7-9, 13-15, and 19-21). This uniformed protocol was then suited to forge advanced bis-tetrahydrofuran, bis-pyrrolidine, and bis-thiolane scaffolds encompassing the heterocyclic core portion of various binuclear annonaceous acetogenins and relatives. The utility of this synthesis was demonstrated by the preparation of a repertoire of eight isomeric bis-tetrahydrofuran units, 41-48, two bis-pyrrolidine units, 62 and 63, and four bis-thiolane units, 78-81.
authors.affiliation: Dipartimento Farmaceutico, Università di Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Zanardi
authors.forename: L
authors.initials: L
authors.lastname: Battistini
authors.forename: G
authors.initials: G
authors.lastname: Rassu
authors.forename: L
authors.initials: L
authors.lastname: Auzzas
authors.forename: L
authors.initials: L
authors.lastname: Pinna
authors.forename: L
authors.initials: L
authors.lastname: Marzocchi
authors.forename: D
authors.initials: D
authors.lastname: Acquotti
authors.forename: G
authors.initials: G
authors.lastname: Casiraghi
mesh_terms: D005663:Furans / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D005663:Furans; D011758:Pyrroles; D013876:Thiophenes