Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. III. Synthetic study of rhodopeptins.
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 beta-amino acid moiety, were achieved. The beta-amino acid moiety was prepared as a racemate by the thermal Michael addition of an amine to alpha,beta-unsaturated ester. The racemic beta-amino acids were converted to their L-Valylamide derivatives and the obtained diastereomers were separated. Coupling of both diastereomers, L-Val-beta-amino acids with Gly-L-Lys gave linear tetrapeptides, and tetrapeptides were cyclized by diphenylphosphoryl azide (DPPA) method between C-terminus of beta-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 beta-amino acid moiety in natural rhodopeptin B5 has (R)-configuration.
Chiba
H
H
Process Development Laboratories, Mercian Corporation, Iwata-shi, Shizuoka, Japan.
Agematu
H
H
Sakai
K
K
Dobashi
K
K
Yoshioka
T
T
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D012240:Rhodococcus / Q000378:metabolism; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; C401241:LV9nA; D010456:Peptides, Cyclic; C401441:rhodopeptin B5