Solution- and solid-phase synthesis of natural product-like tetrahydroquinoline-based polycyclics having a medium size ring.
A solid-phase synthesis of tetrahydroquinoline-derived polycyclic 4, having a medium size ring with an enamide functionality, was achieved from tetrahydroquinoline derivative 3 in five steps with overall 40-45% yield. An enantiopure, tetrahydroquinoline-derived beta-amino ester, 1, was converted into compound 2 that has a free phenolic hydroxyl group as an anchoring site for solid-phase synthesis. The solid-phase worked well for this sequence, in which the synthesis of the unsaturated eight-membered enamide lactam was obtained by a ring-closing metathesis approach. Compound 4 is a novel, natural product-like polycyclic derivative that could further be utilized in library generation for developing small molecule chemical probes.
Arya
Prabhat
P
Chemical Biology Program, Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6. Prabhat.Arya@nrc.ca
Couve-Bonnaire
Samuel
S
Durieux
Patricia
P
Laforce
Daisy
D
Kumar
Rohtash
R
Leek
Donald M
DM
D001688:Biological Products / Q000737:chemistry*; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D012117:Resins, Synthetic; D012996:Solutions; D013237:Stereoisomerism
D001688:Biological Products; D011083:Polycyclic Compounds; D011804:Quinolines; D012117:Resins, Synthetic; D012996:Solutions; C037219:quinoline