title: Unexpected syntheses of seco-cyclopropyltetrahydroquinolines - from a radical 5-exo-trig cyclization reaction: analogs of CC-1065 and the duocarmycins.
abstract: Analogs of the seco-cyclopyrroloindoline (seco-CPI), the DNA alkylation pharmacophore of CC-1065 and the duocarmycins, can be prepared through a 5-exo-trig radical cyclization of a free radical and a 3-chloro-2-allylic moiety. This manuscript reports an unexpected discovery that, depending on the structure and stability of the free radical, the cyclization process leads to the production of an appreciable amount of seco- cyclopropyltetrahydroquinolines 7a-d along with the seco-cyclopropoyltetra- hydroindoline products (6a-e). For instance, free radical reaction of the bromoallylic chloride 5a produced an equal amount of 6-benzyloxy-N-t-butoxycarbonyl-3- (chloromethyl)furano[e]indoline (6a), and 7-benzyloxy-N-t-butoxycarbonyl-3-chloro- 1,2,3,4-tetrahydrofurano[f]quinoline (7a). Three other examples that produced mixtures of indoline and quinoline products are provided. In only one of the examples reported in this manuscript, the 6-benzyloxy-N-t-butoxycarbonyl-3-(chloromethyl)benzo[e]indoline, was a seco-CBI precursor 6e formed exclusively, consistent with literature precedents.
authors.affiliation: Department of Chemistry, Furman University, Greenville, SC 29613, USA.
authors.forename: Hari
authors.initials: H
authors.lastname: Pati
authors.forename: Tiffany
authors.initials: T
authors.lastname: Howard
authors.forename: Heather
authors.initials: H
authors.lastname: Townes
authors.forename: Brian
authors.initials: B
authors.lastname: Lingerfelt
authors.forename: LuAnne
authors.initials: L
authors.lastname: McNulty
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000080890:Duocarmycins; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003521:Cyclopropanes; D000080890:Duocarmycins; D007211:Indoles; D011758:Pyrroles; D011760:Pyrrolidinones; C110747:cyclopropapyrroloindole; C057901:pyrindamycin B; C066098:duocarmycin SA; C018782:CC 1065; C058289:duocarmycin A