Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp.. III. Synthetic study of rhodopeptins

Article abstract of DOI:10.7164/antibiotics.52.710

Total syntheses of cyclo (-Gly-L-Lys-L-Val-(R)-3-aminododecanoyl-); LV9nA and its diastereomer cyclo (-Gly-L-Lys-L-Val-(S)-3-aminododecanoyl-); LV9nB, congeners of rhodopeptin B5 on β-amino acid moiety, were achieved. The β-amino acid moiety was prepared as a racemate by the thermal Michael addition of an amine to α,β-unsaturated ester. The racemic β-amino acids were converted to their L-Valylamide derivatives and the obtained diastereomers were separated. Coupling of both diastereomers, L-Val-β-amino acids with Gly-L-Lys gave linear tetrapeptides, and tetrapeptides were cyclized by diphenylphosphoryl azide (DPPA) method between C-terminus of β-amino acid and N-terminus of Gly to give cyclic tetrapeptides. The deprotected cyclic tetrapeptides, LV9nA and LV9nB, both exhibited almost the same antifungal activity as the naturally obtained rhodopeptins. Furthermore, comparison of the ¹H NMR spectra of two congeners and rhodopeptin B5 suggested that the stereochemistry of β-amino acid moiety in natural rhodopeptin B5 has (R)-configuration.