An improved synthesis of (20R,22R)-cholest-5-ene-3beta,20,22-triol, an intermediate in steroid hormone formation and an activator of nuclear orphan receptor LXR alpha.
Asymmetric dihydroxylation of (20(22)E)-cholesta-5,20(22)-dien-3beta-ol acetate (2a), prepared from pregnenolone, gave a 1:1 mixture (67% yield) of (20R,22R)-cholest-5-ene-3beta,20,22-triol 3-acetate (3a) and its 20S,22S isomer 3b. Highly purified 3a and 3b were obtained by semipreparative silver ion high performance liquid chromatography. Saponification of 3a and 3b gave (20R,22R)-cholest-5-ene-3beta,20,22-triol (4a) and its 20S,22S isomer 4b. This simple approach provided the natural isomer 4a more efficiently than previously described chemical or enzymatic syntheses. Full 1H and 13C nuclear magnetic resonance data were presented for triols 4a and 4b and their synthetic precursors. Side-chain conformations of 2a, its 20(22)Z isomer, 4a, and 4b were studied by molecular mechanics and nuclear Overhauser effect difference spectroscopy.
Ruan
B
B
Department of Chemistry, Rice University, Houston, Texas 77005, USA.
Wilson
W K
WK
Schroepfer
G J
GJ
D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000071518:Liver X Receptors; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors; D011284:Pregnenolone / Q000096:biosynthesis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C003563:20,22-dihydroxycholesterol; D011284:Pregnenolone