Isolation and synthesis of novel farnesyl protein transferase inhibitors, valinoctins A and B, from Streptomyces strain MJ858-NF3.
Two novel farnesyl protein transferase inhibitors, valinoctins A (1) and B (2), were isolated from the fermentation broth of Streptomyces strain MJ858-NF3. The tentative structures of these compounds were elucidated from NMR and mass spectra as dipeptides consisting of valine and a novel amino acyl moiety. Four possible isomers of valinoctin A were synthesized, and the protected derivative of the appropriate compound was crystallized to give the relative stereochemistry of X-ray analysis. Since the valine residue of valinoctin A was determined to be the L-configuration by a chiral HPLC column, absolute configuration of valinoctin A was determined.
Sekizawa
R
R
Department of Applied Chemistry, Keio University, Kanagawa, Japan.
Iinuma
H
H
Muraoka
Y
Y
Naganawa
H
H
Kinoshita
N
N
Nakamura
H
H
Hamada
M
M
Takeuchi
T
T
Umezawa
K
K
D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000378:metabolism*
D004151:Dipeptides; D004791:Enzyme Inhibitors; C102702:valinoctin A; C102703:valinoctin B; D010458:Peptidyl Transferases