Synthesis of an isomeric mixture (24RS,25RS) of sodium scymnol sulfate.
This is the first reported multistep synthesis of the shark bile sterol sodium scymnol sulfate epimeric at the C-24 hydroxyl and C-27 sulfate positions. The starting cholic acid was protected as the tetrahydropyran ether (THP) derivative, reduced to the C-24 alcohol and oxidized to the protected aldehyde. This aldehyde was then coupled with methyl 3-hydroxypropionate using 2equiv. of lithium diethylamide at -65 degrees C to produce methyl (24RS,25RS)-24,27-dihydroxy-3alpha,7alpha,12alpha,tris[(tetrahydropyran-2-yl)oxy]-5beta-cholestan-26-oate. After protecting the 24 and 27 hydroxyls as the THP derivatives, this fully protected ester was then reduced to the monoalcohol. The monoalcohol was sulfated using the sulfur trioxide-triethylamine complex in dimethylformamide. The protective THP groups were removed with methanolic HCl and the sulfate was converted to the sodium salt with sodium ethoxide in methanol. This general synthetic scheme has application to produce a range of monosulfated sterols.
Harney
Donald W
DW
Natural Products Research Group, School of Medical Sciences, RMIT University, PO Box 71, Bundoora 3083, Victoria, Australia.
Macrides
Theodore A
TA
D002777:Cholestanols / Q000138:chemical synthesis* / Q000737:chemistry*; D019826:Cholic Acid / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D002777:Cholestanols; C059448:scymnol sulfate ester; D019826:Cholic Acid