Michael Pyerin

Asymmetric synthesis of (+)- and (−)-7-(3-pyridyl)-1-azabicyclo[2.2.1]heptane as conformationally restricted analogues of nicotine

Both enantiomers of the conformationally restricted nicotine analogue 7-(3-pyridyl)-1-azabicyclo[2.2.1]heptane were prepared in a convenient, asymmetric synthetic route.

A New Route to 4-Ethynyl-N-hydroxy-2-imidazolidinones via Oxime Addition

Abstract A rapid route was developed to afford ethynyl-substituted imidazole derivatives which served as key compounds for aryl–alkynyl-coupling reactions. Addition of mono-silylated acetylene to O-protected oximes was carried out in the absence of Lewis acids, directly affording the title compounds 3a–c in a one-pot reaction. Limitations and dependence of the feasibility on N1-substituents are discussed.

Synthesis of Substituted Alkoxythiophenes: Thiophene Analogues of Dazoxiben

Summary. The synthesis of the thiophene analogue of dazoxiben – one of the most selective TXA2-synthase inhibitors – and its derivatization to a chlorinated, more lipophilic product is described. The ethylenoxy moiety was introduced via nucleophilic aromatic substitution of halogenated thiophene carboxylic esters, the imidazol residue, by use of a t-butoxy group as a synthon after ether cleavage and halogenation. Also, at this step chlorination of the thiophene moiety was carried out. After ester hydrolysis the target compounds were obtained as hydrochlorides.Zusammenfassung. Die Synthese des Thiophenanalogons von Dazoxiben – eines hoch selektiven TXA2-Synthase-Inhibitors – und seine Derivatisierung zu einem chlorierten, stärker lipophilen Produkt wird beschrieben. Die Ethylenoxy-Gruppierung wurde durch nucleophile aromatische Substitution von halogenierten Thiophencarbonsäureestern eingeführt, Imidazol unter Verwendung einer t-Butoxygruppe als Synthon (nach Etherspaltung und Halogenierung). Auf dieser Stufe erfolgte außerdem die Chlorierung am Thiophenteil. Nach Esterhydrolyse wurden die Zielverbindungen als Hydrochloride erhalten.

A Facile Route to Functionalized Cyclopenta[b]thiophenones Based on the Structure of the Selective COX-2 Inhibitor Flosulide

Summary. The synthesis of three thiophene analogues of Flosulide – a potent and selective inhibitor of cyclooxygenase subtype 2 (COX-2) – is described. Utilizing combined Friedel-Crafts acylation and alkylation of 2-chlorothiophene, simplified procedures were developed to obtain cyclopenta[b]- thiophenones as key products which were further derivatized by nitration, nucleophilic aromatic substitution, reduction, and mesylation.Zusammenfassung. Die Synthese dreier Thiophenanaloga von Flosulid – ein potenter und selektiver Hemmer der Cyclooxygenase vom Subtyp 2 (COX-2) – wird beschrieben. Durch Anwendung kombinierter Friedel-Crafts-Acylierung und -Alkylierung von 2-Chlorthiophen wurden vereinfachte Verfahren zur Herstellung von Cyclopenta[b]thiophenen als Schlüsselsubstanzen entwickelt, welche weiter durch Nitrierung, nucleophile aromatische Substitution, Reduktion und Mesylierung derivatisiert wurden.

(3aR,8bR)-(+)-1-Methyl-1,2,3,3a,4,8b-hexa­hydro­pyrrolo[2′,3′:3,4]cyclo­penta[1,2-b]pyridine-1,5-diium dichloride monohydrate

The title compound, C11H16N22+·2Cl−·H2O, is a novel conformationally constrained tricyclic analogue of nicotine, in which the pyridine and pyrrolidine rings of the latter are bridged by a CH2 group. As result of this bridge, these two rings are no longer approximately perpendicular as in various salts of nicotine.