Diastereoselective synthesis of octahydro-14H-benzo[g]quinolino-[2,3-a]quinolidines. Improved cytotoxic activity against human brain tumor cell lines as a result of the increased rigidity of the molecular backbone.
Cis-Octahydro-14H-benzo[g]quinolino[2,3-a]quinolidines 6 were obtained in 6 steps from L-phenylalanine. The key step utilizes a diastereoselective intramolecular EtAlCl2-catalyzed hetero-Diels-Alder reaction. Compounds 6a-f were tested in vitro against human medulloblastoma D283 Med and glioblastoma A-172 and T98G cell lines and showed improved cytotoxicity compared to the corresponding, less rigid pyrido[1,2-b]isoquinolines 1.
Monsees
A
A
Institut für Organische Chemie der Technischen Universität Braunschweig, Germany.
Laschat
S
S
Hotfilder
M
M
Jones
P G
PG
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001932:Brain Neoplasms / Q000473:pathology; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011804:Quinolines