Synthesis of Acidiphilamides A–C

Synthesis of Acidiphilamide A–C: Secondary Metabolites from the Genus Streptacidiphilus: P. Mallesham; K. Raghavulu, V. Miriyala, R. Doddipalla, S. Yennam, P. D. Sanasi, M. Behera
SynOpen 2023, 7, 130–139; DOI: 10.1055/a-2035-9753

In 2019, five novel tripeptide metabolites, acidiphilamides A–E, were identified in Streptacidiphilus acidic forest soil. Based on NMR and mass spectroscopy data, the structures of these natural compounds were identified as containing phenylalaninol or methioninol fragments. The group of Dr. Manoranjan Behera from Aragen Life Sciences (Hyderabad, India) has recently reported the total synthesis of acidiphilamides A–C and epi-acidiphilamides A–C from commercially available l-phenyl alanine using hexafluorophosphate azabenzotriazole tetramethyl uronium (HATU) as peptide coupling reagent. The structures of the synthetic acidiphilamides A, B and C were characterized by NMR, MS and Specific Optical Rotation data, and were shown to match those of the natural products, whereas the structures of epi-acidiphilamides A, B and C were confirmed by 2D NMR studies.

Dr. Behera said: “The total synthesis of acidiphilamides A–C and its epi isomers has been achieved for the first time and the spectroscopic data were compared to provide insight into the correct stereochemistry of the natural products. This will help medicinal chemists to study the structure–activity relation (SAR) of acidiphilamide A–C derivatives as autophagy inhibitors, as these compounds can be synthesized in gram quantity.”