The synthesis and in vitro activity of some delta 7,9(11)-lanostadienes.
The synthesis of delta 7,9(11)-lanostadiene derivatives functionalized at C(32) starting from 3 beta-acetoxy-7 alpha,32-epoxylanostan-11-one has been presented. The delta 7,9(11) moiety was efficiently introduced in three steps in 71% yield by the regioselective abstraction of allylic 8 beta hydrogen. The formyl group of the key intermediate, 3 beta-benzoyloxylanosta-7,9(11)-dien-32-al, has been stereoselectively alkylated into (32S) derivative, whereas its oxidation unexpectedly afforded 3 beta-benzoyloxy-7-oxolanost-8-ene-32,11 alpha-lactone and not the corresponding acid. delta 7,9(11)-lanostadienes possessing HC(32)=O, C(32) [symbol: see text] N, HC(32S)CH3OH, H2C(32)OH, as well as some 11-keto lanostenes, were tested in vitro against several purified cholesterogenic enzymes showing moderate activity, with most the active aldehyde 16 having IC50 = 86 microM.
Solaja
B A
BA
Faculty of Chemistry, University of Belgrade, Yugoslavia. bsolaja@hf01.chem.bg.ac.yu
Dermanović
M
M
Lim
D M
DM
Paik
Y K
YK
Tinant
B
B
Declerq
J P
JP
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D015394:Molecular Structure; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D058886:Sterol 14-Demethylase
C110024:3-hydroxylanosta-7,9(11)-dien-32-al; D000924:Anticholesteremic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007810:Lanosterol; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase