Cyclization of Free Radicals at the C-7 Position of Ethyl Indole–2-carboxylate Derivatives: an Entry to a New Class of Duocarmycin Analogues

Naim H Al-Said,Wasim N Abdullah,Khaled Q Shawakfeh

doi:10.3390/10121446

Naim H Al-Said, Wasim N Abdullah + Show 1 more

Open Access

https://doi.org/10.3390/10121446

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Abstract

Aryl free-radicals generated at the C-7 position of ethyl indole-2-carboxylates bearing N-allyl and propargylic groups triggered intramolecular cyclizations to furnish a new class of Duocarmycin analogues, formal ethyl pyrrolo[3,2,1-ij]quinoline-2-carboxylate derivatives, through the less favorable 6-endo-trig cyclization mode.

Highlights

In the course of our research aimed at the synthesis of biologically active simple pharmacophores of structurally complex natural products [1,2], we turned our attention to the duocarmycins (1-6, Figure 1) [3,4,5,6,7]
These compounds are natural potent antitumor antibiotics that have drawn a great deal of attention [8,9,10]. Their cytotoxicity is directly related to the chemical stability of these compounds in aqueous acidic solutions and it is believed that this stability is mainly due the vinylogous amide conjugation, which is disrupted after binding to the DNA
As a prelude to biological evaluation, we describe the cyclizations of aryl free radicals generated at the C-7 position of N-allylic and N-propargylic substituted ethyl 7-haloindole-2-carboxylates that provided pyrroloquinoline derivatives through an 6-endo cyclization mode

Summary

Introduction

In the course of our research aimed at the synthesis of biologically active simple pharmacophores of structurally complex natural products [1,2], we turned our attention to the duocarmycins (1-6, Figure 1) [3,4,5,6,7].

Results

Conclusion