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Fragments of Peptoid 1:Synthesis of N-Substituted Glycine Monomers
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1  Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn

Published: 01 November 2017 by MDPI in 3rd International Electronic Conference on Medicinal Chemistry session ECMC-3

Peptoids are N-substituted glycine oligomers comprising multiple biomedical applications. In particular, they are used in nanotechnological approaches. In this context, their application is typically focused on larger oligomers, which form two-dimensional structures, but are difficult to be synthesized. However, a short peptoid of three N-substituted glycine building blocks, referred to as peptoid 1, is known to inhibit the proapoptotic protein APAF1. Herein, we report on the preparation of various peptoidic building blocks of peptoid 1. The synthesis was conducted by alkylation of two different amine components, 2-(2,4-dichlorophenyl)ethylamine and 3,3-diphenylpropylamine with tert-butyl bromoacetate, benzyl bromoacetate, and 2-bromoacetamide, respectively. The resulting glycine derivatives have been characterized by NMR and LC/MS data. The new peptoid units will be provided to biochemical studies, e.g. to the evaluation of protease-inhibiting properties, in order to perform a fragment-based approach.

Keywords: peptoids; building blocks; N-alkylations
Comments on this paper
Andrea Porcheddu
nice job!
A curiosity, is it possible to increase the yields of 7 by using chloroacetonitrile instead of 2-bromoacetamide? Why the final compounds are only purified by chromatography and not by using a classic aqueous acid-base work-up?


Franziska Kohl
Dear Professor Porcheddu,
Thank you for this suggestion. We did not try to react compound 1 with chloroacetonitrile so far. But this approach would finally lead to a nitrile analogous of peptoid 1, which might possess interesting biological activities.
Concerning the work up, you are right. We have first extracted the crude products and washed the organic layers. Basic products were extracted with dichloromethane after addition of 0.1 N NaOH prior to column chromatography. The N-protected products were extracted with dichloromethane after addition of sat. NaHCO3 or water and brine, respectively, prior to column chromatography.

Best wishes
Franziska Kohl