Synthesis of Cholesterol

Structure of Cholesterol

C27H46O

Principal investigatorRobert B. Woodward
Publication year1951
Synthesis typeFormal
Number of steps 35 (linear)
References
Part 1 of 1
intermediate structure
1,3-Butadiene
PhH
100 °C, 96 h, 86%
intermediate structure
NaOH
Dioxane , H2O
40-50 °C, , 90%
intermediate structure
LiAlH4
THF
Reflux, 65 min, 64%
intermediate structure
H2SO4
Dioxane , H2O
RT, 24 h, 99%
intermediate structure
Ac2O
Pyr
RT, 12 h, 96%
intermediate structure
Zn
Ac2O
Reflux, 8 min, 63%
intermediate structure
HCO2Et, NaOMe
PhH
RT, 30 min, 94%
intermediate structure
Ethyl vinyl ketone, KOt-Bu, NaOH
t-BuOH, H2O
0 °C to RT, 10 h, 53%
intermediate structure
KOH
Dioxane , H2O
0 °C, 3 h, 88%
intermediate structure
OsO4
Et2O
0 °C, 5-8 d, 57%
"A single, uncharacterized isomer was isolated."
intermediate structure
CuSO4
Acetone
RT, 36 h, 83%
intermediate structure
H2, Pd/SrCO3
PhH
RT, 3.5 h, 85%
intermediate structure
HCO2Et, NaOMe
PhH
RT, ON
intermediate structure
PhNHMe
MeOH
RT, 24 h, 88% (2 steps)
intermediate structure
VinylCN, Me3N+Bn HO-
PhH, t-BuOH, H2O
50 °C, 45 h
intermediate structure
KOH
H2O
Reflux, , 46% (2 steps)
"Also isolated was the C1-epimer (33 % yield)."
intermediate structure
NaOAc
Ac2O
Reflux, 2 h, 28%
intermediate structure
MeMgBr
PhH, Et2O
-18 °C, 3 h
intermediate structure
NaOH
MeOH, H2O
Reflux, 2 h, 58% (2 steps)
intermediate structure
HIO4
Dioxane , H2O
0 °C, 14 h
intermediate structure
Piperidine, AcOH
PhH
60 °C, 60 min, 66% (2 steps)
intermediate structure
Na2Cr2O7
AcOH, H2O
RT, 10 h
intermediate structure
CH2N2
PhH, Et2O
RT, 20 min, 30% (2 steps)
intermediate structure
H2, PtO2
AcOH
RT
intermediate structure
CrO3
AcOH
RT, ON, 2.4% (2 steps)
intermediate structure
NaBH4
EtOH
RT, 4 h, 64%
intermediate structure
KOH
MeOH, H2O
Reflux, 12 h, 100%
intermediate structure
Ac2O
Pyr
60 °C, 3 h, 92%
intermediate structure
SOCl2
0 °C to RT, 15.5 h, 90%
intermediate structure
MeCd
PhH
Reflux, 90 min, 92%
intermediate structure + intermediate structure
PhH, Et2O
RT, 60 min
intermediate structure
Ac2O
AcOH
Reflux, 2.5 h
intermediate structure
H2, PtO2
AcOH
RT, 30 min, 14% (3 steps)
intermediate structure
KOH
MeOH, H2O
Reflux, 2 h, 85%
intermediate structure
Remaining...
(5 steps)
"See : Org. Synth. 1937, 17, 43; Ber. 1935, 68, 2091; Helv. Chim. Acta 1938, 21, 866; J. Chem. Soc. 1950, 2325."
intermediate structure