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Unexpected Syntheses of seco-Cyclopropyltetrahydroquinolines >From a Radical 5-Exo-Trig Cyclization Reaction: Analogs of CC-1065 and the Duocarmycins

Authors :
Moses Lee
LuAnne McNulty
Brian Lingerfelt
Heather Townes
Lori Forrest
Hari Pati
Source :
Molecules, Vol 9, Iss 3, Pp 125-133 (2004)
Publication Year :
2004
Publisher :
MDPI AG, 2004.

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.

Details

Language :
English
ISSN :
14203049
Volume :
9
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.32b058a0d84f548ddc571d039ea6f0
Document Type :
article
Full Text :
https://doi.org/10.3390/90300125