Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. II. Structure elucidation and total synthesis.
Schizostatin (1) has been isolated as a potent and selective inhibitor of squalene synthase. Its structure has been determined using spectroscopic methods: the compound is shown to be a diterpenoid which has a trans-dicarboxylic acid moiety. Total synthesis of schizostatin (1) was achieved by the highly regio- and stereoselective coupling reaction of an allylic bromide with a barium reagent. The Z-isomer 16 was also prepared using the stereoselective syn-addition of an organocopper reagent to acetylenedicarboxylate.
Kogen
H
H
Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Tago
K
K
Kaneko
S
S
Hamano
K
K
Onodera
K
K
Haruyama
H
H
Minagawa
K
K
Kinoshita
T
T
Ishikawa
T
T
Tanimoto
T
T
Tsujita
Y
Y
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry*; D005650:Fumarates / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012567:Schizophyllum / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005650:Fumarates; C101437:schizostatin; D013186:Farnesyl-Diphosphate Farnesyltransferase