Aryl amidation routes to dihydropyrrolo[3,2-e]indoles and pyrrolo[3,2-f]tetrahydroquinolines: total synthesis of the (+/-)-CC-1065 CPI subunit.
CC-1065 and the related duocarmycins are members of a structurally unique family of naturally occurring molecules and remain some of the most rigorously studied antitumor compounds to date. Herein we describe a total synthesis of the (+/-)-CC-1065 CPI subunit in an overall yield of 9.3% from commercially available 5-fluoro-2-nitrophenol. The key steps of this synthesis are a Diels-Alder reaction of an o-benzoxy-monoimine quinoid and an intramolecular aryl triflate amidation, which formed the pyrrolo[3,2-f]tetrahydroquinoline intermediate en route to CPI.
Ganton
Michael D
MD
Department of Chemistry, The University of Western Ontario, London, Ontario, Canada, N6A 5B7.
Kerr
Michael A
MA
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000080890:Duocarmycins; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D000080890:Duocarmycins; D007211:Indoles; D011804:Quinolines; C018782:CC 1065