A concise total synthesis of (-)-quinocarcin via aryne annulation.
Described in this report is a rapid asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic (-)-quinocarcin. The sequence employs a mild fluoride-induced aryne annulation developed in our laboratories to build a key isoquinoline-containing intermediate comprising the entire carbon scaffold of the natural product. This intermediate is advanced through six additional steps to the target alkaloid, providing the shortest synthetic route to (-)-quinocarcin reported to date.
Allan
Kevin M
KM
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Stoltz
Brian M
BM
D000470:Alkaloids / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry; D002621:Chemistry / Q000379:methods; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005459:Fluorides / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008956:Models, Chemical; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000737:chemistry
D000470:Alkaloids; D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D002244:Carbon; C038710:quinocarcin; D005459:Fluorides