Racemization-free synthesis of Nα-2-thiophenoyl-phenylalanine-2-morpholinoanilide enantiomers and their antimycobacterial activity
Autor: | René Csuk, Jan Henrik Halz, Sophie Hoenke, Markus Lang, Adrian Richter, Philipp Schulze, Lea Mann, Rüdiger W. Seidel |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
medicine.drug_class
Stereochemistry Phenylalanine Clinical Biochemistry Microbial Sensitivity Tests Antimycobacterial Biochemistry Mycobacterium 03 medical and health sciences chemistry.chemical_compound Amide medicine GSK1055950A Racemization-free synthesis Phenylalanine amides Racemization Chromatography High Pressure Liquid 030304 developmental biology MMV688845 0303 health sciences Calorimetry Differential Scanning 030306 microbiology Hydrogen bond Enantioselective activity Crystal structure Spectrum Analysis Organic Chemistry Stereoisomerism Amino acid chemistry Antimycobacterial activity Original Article Enantiomer Lead compound Derivative (chemistry) |
Zdroj: | Amino Acids |
ISSN: | 1438-2199 0939-4451 |
Popis: | Nα-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide (MMV688845, IUPAC: N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide) from the Pathogen Box® library (Medicines for Malaria Ventures, MMV) is a promising lead compound for antimycobacterial drug development. Two straightforward synthetic routes to the title compound starting from phenylalanine or its Boc-protected derivative are reported. Employing Boc-phenylalanine as starting material and the T3P® and PyBOP® amide coupling reagents enables racemization-free synthesis, avoiding the need for subsequent separation of the enantiomers. The crystal structure of the racemic counterpart gives insight into the molecular structure and hydrogen bonding interactions in the solid state. The R-enantiomer of the title compound (derived from d-phenylalanine) exhibits activity against non-pathogenic and pathogenic mycobacterial strains, whereas the S-enantiomer is inactive. Neither of the enantiomers and the racemate of the title compound shows cytotoxicity against various mammalian cells. |
Databáze: | OpenAIRE |
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