title: Part 1. modular approach to obtaining diverse tetrahydroquinoline-derived polycyclic skeletons for use in high-throughput generation of natural-product-like chemical probes.
abstract: A practical synthesis of a tetrahydroaminoquinoline scaffold (12) was developed that used a stereocontrolled aza Michael as the key reaction. Three tetrahydroquinoline alkaloid-like, tricyclic derivatives 16, 18, and 19 with different medium to macrocyclic ring skeletons were obtained, using this scaffold as the starting material, in a modular manner. The macrocyclic compounds with an isolated olefin and an electron-deficient olefin were obtained by ring-closing metathesis approaches. Compounds 16 and 18 are unique and contain bridged 10- and 12-membered functionalized rings. The NMR studies of these compounds revealed interesting information on the conformation of the bicyclic scaffolds that was dependent on the nature and the size of the macrocyclic rings. Finally, this modular methodology, using compound 21 anchored onto the solid support, successfully led to the generation of different macrocyclic derivatives, 23, 25, and 27 in solid-phase synthesis. The solid-phase synthesis approach outlined in this article has the potential to generate tetrahydroquinoline-based tricyclic compounds containing different medium to macrocyclic architectures.
authors.affiliation: Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Michael
authors.initials: M
authors.lastname: Prakesch
authors.forename: Utpal
authors.initials: U
authors.lastname: Sharma
authors.forename: Maya
authors.initials: M
authors.lastname: Sharma
authors.forename: Shahriar
authors.initials: S
authors.lastname: Khadem
authors.forename: Donald M
authors.initials: DM
authors.lastname: Leek
authors.forename: Prabhat
authors.initials: P
authors.lastname: Arya
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D006912:Hydroxyquinolines / Q000138:chemical synthesis / Q000737:chemistry*; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D006912:Hydroxyquinolines; D015335:Molecular Probes; D011083:Polycyclic Compounds