General Papers
ARKIVOC 2016 (iv) 339-351
Synthesis of Nα-protected aminoacid/peptide Weinreb amides employing N,N'-carbonyldiimidazole as activating agent; studies on docking and antibacterial activities K. Uma,a H.S. Lalithamba,*a M. Raghavendra,a Vivek Chandramohan,b and C. Anupama b a Department
of Chemistry, Siddaganga Institute of Technology, B.H. Road, Tumakuru-572 103, Karnataka, India b Department of Biotechnology, Siddaganga Institute of Technology, B.H. Road, Tumakuru-572 103, Karnataka, India Email:
[email protected] DOI: http://dx.doi.org/10.3998/ark.5550190.p009.605 Abstract
An efficient method for the synthesis of Nα-protected amino/ peptide Weinreb amides (Nmethoxy-N-methylamides) employing N,N'-carbonyldiimidazole (CDI) has been achieved. Nαprotected amino/peptide acids were treated with N,N'-carbonyldiimidazole, followed by the addition of N,O-dimethylhydroxylamine hydrochloride salt to yield the desired compounds. The synthesized compounds were mainly gums, a few were solids, after the simple workup, and were characterized by IR, 1H NMR, 13C NMR and HRMS. The Weinreb amides were subjected to in silico studies, to predict the preferred orientation and binding affinity between the molecules using scoring functions. The ligand N-Fmoc-L-Phe-N(OCH3)CH3 showed minimum binding energy 29.85 kcal/mol with Escherichia coli and the ligand N-Fmoc-L-Ala-N(OCH3)CH3 showed minimum binding energy -24.79 kcal/mol with Pseudomonas aeruginosa, -25.01 kcal/mol with Staphylococcus aureus. Based on the minimum binding energies, antibacterial activities have been conducted for a few of the synthesized compounds. Key words: Weinreb amides, N,O-dimethylhydroxylamine hydrochloride, N,N'-carbonyldiimidazole, in silico molecular docking studies, in vitro antibacterial activities
Introduction Weinreb amides have wide importance in organic synthesis due to their versatile reactivity with nucleophiles and selective reduction to aldehydes. Weinreb amides derived from amino acids have been extensively used as precursors in the preparation of α-amino aldehydes and α-amino ketones. They are selectively reduced to aldehydes using LiAlH4 and form ketones upon reaction with Page 339
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