Stereospecific synthesis of a novel farnesyl protein transferase inhibitor, valinoctin A and its analogues.
(2S,3R)-3-Amino-2-hydroxyoctanoic acid was synthesized by Curtius rearrangement of an azide derivative of (S)-malic acid. Total syntheses of valinoctin A and its analogues were achieved by a coupling of (2S, 3R)-3-amino-2-hydroxyoctanoic acid moiety with L-valine or several other amino acids moieties. 2S configuration of 3-amino-2-hydroxyoctanoic acid moiety was found to be important for the inhibitory activity and the L-valine moiety of valinoctin A was exchangeable with other L-amino acids.
Tsuda
M
M
Institute of Microbial Chemistry, Tokyo, Japan.
Muraoka
Y
Y
Takeuchi
T
T
Sekizawa
R
R
Umezawa
K
K
D019883:Alkyl and Aryl Transferases; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D014166:Transferases / Q000037:antagonists & inhibitors*
D004151:Dipeptides; D004791:Enzyme Inhibitors; C102702:valinoctin A; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase