Total synthesis of ent-cholesterol via a steroid C,D-ring side-chain synthon.
For the first time, one of the two enantiomers of cholesterol (ent-cholesterol) has been synthesized by a synthetic route that starts from a precursor containing the D-ring and entire side chain of cholesterol. As part of the reported synthetic route, a method of general utility for the large scale (>10 g) preparation of each enantiomer of [1 alpha(R*),7a alpha]-1-(1,5-dimethylhexyl)-1,2,3,6,7,7a-hexahydro-7a-methyl-5H-inden-5-one, C,D ring-side chain synthons that can be used for the synthesis of enantiomers of vitamin D(3), cholesterol, and their analogues was also developed. Using the enantiomer of the C,D-ring side-chain synthon that leads to ent-cholesterol, the A- and B-rings were elaborated from a linear fragment that is sequentially cyclized to form the steroid B- and A-rings. Using this route, ent-cholesterol was prepared in 23 steps from the methyl ester of (1 alpha,5 alpha,6 alpha)-(+/-)-6-methyl-2-oxo-bicyclo[3.1.0]hexane-1-carboxylic acid in a total yield of 2.6%.
Jiang
Xin
X
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Covey
Douglas F
DF
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
D002784:Cholesterol