Microwave-Assisted Synthesis ofN-Heterocycles and Their Evaluation Using an Acetylcholinesterase Immobilized Capillary Reactor

Diego P Sangi,Kenia L Vanzolini,Julia L Monteiro,Marcio W Paixão,Arlene G Corrêa,Quezia B Cass

doi:10.5935/0103-5053.20140056

Diego P Sangi, Kenia L Vanzolini + Show 4 more

Open Access

https://doi.org/10.5935/0103-5053.20140056

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Abstract

Polarized ketene dithioketals have been recognized as useful building blocks in many synthetic operations. In this work, a transition-metal-free annulations of 1,1-bis(thiomethyl)-2-nitroethylene with hydroxylalkylamines or alkyldiamines have been reported. This methodology provides a directed approach to N-heterocycles, e.g., imidazolidines, oxazolidines and benzoxazoles under microwave conditions. These compounds were evaluated as acetylcholinesterase inhibitors by using an enzyme immobilized capillary reactor-tandem mass spectrometry.

Highlights

Association of biological activity with heterocyclic motifs is well known and is an important strategy in drug discovery programs
The ketene dithioketals have been employed as intermediates for the synthesis of several
As part of our studies on ketene dithioacetal for the synthesis of heterocycles, we have found that microwave irradiation accelerates the vinylic substitution of nitroketene S,S-acetals with anilines and amines using ethanol as solvent.[9]

Summary

Introduction

Association of biological activity with heterocyclic motifs is well known and is an important strategy in drug discovery programs. N-heterocycles, which present different biological properties, such as enzyme inhibition,[3,4] insecticides,[5] and tuberculostatic activity.[6] More recently, the bis-vinylic substitution of 1,1-bis(methylthio)-2-nitroethylene with diamines or hidroxylamines has been reported for the synthesis of 5-member or 6-member nitrovinyl derivatives.[7]

Results

Conclusion