Synthesis of Cholesterol

Structure of Cholesterol

C27H46O

Principal investigatorRobert Robinson
Publication year1953
Synthesis typeFormal
Number of steps 68 (linear)
References
J. Chem. Soc. 1953, 361. Chem. Ind. 1951, 389. J. Chem. Soc. 1946, 676. J. Chem. Soc. 1949, 1855.
Part 1 of 1
intermediate structure
Me2SO4, NaOH
H2O
RT to 100 °C
See the Williamson Ether Synthesis
intermediate structure
Na
EtOH
Reflux
See the Birch Reduction
intermediate structure
HCl
Dioxane , H2O
RT, 30 min, 71% (3 steps)
intermediate structure
MeI, NaOMe
MeOH
RT to Reflux, 2 h, 50% (53% BRSM)
intermediate structure + intermediate structure
KOEt
EtOH, PhH
0 °C to RT, 2 h, 71%
See the Robinson Annulation
intermediate structure
HI
AcOH, H2O
Reflux, 30-35 min, 58% (70% BRSM)
intermediate structure
PtO2, H2
1 atm
EtOH
RT, 65%
intermediate structure
KOAc, Ac2O
AcOH
Reflux, 1 h, 62% (95% BRSM)
intermediate structure
H2, Pd/SrCO3
150 atm
Dioxane
190-205 °C, 3 h, 63%
intermediate structure
AcOH, CrO3
H2O
RT, 22 h
See the Jones Oxidation
intermediate structure
KOH
EtOH, H2O
Reflux, 60 min, 62% (2 steps)
intermediate structure + intermediate structure
Pyr
120 °C, 2 h, 9%
"Also isolated was other diastereomers (68% yield). The enantiomers were resolved with (-)-brucine."
intermediate structure
KOH
H2O
100 °C, 20 min
"No yield reported."
intermediate structure
NaOMe, HCO2Et
PhH
RT, ON
See the Claisen Condensation
intermediate structure
K2CO3, MeI
Acetone
Reflux, 20 h
intermediate structure
KOH
MeOH
RT, 10 min
intermediate structure
CrO3
AcOH, H2O
RT, 24 h, 32% (4 steps)
See the Jones Oxidation
"First relay molecule."
intermediate structure
Br2, HBr
AcOH, H2O
RT, 41%
"See: Helv. Chim. Acta 1950, 56, 389."
intermediate structure
Pyr
6 h, 62%
"See: Helv. Chim. Acta 1950, 56, 389."
intermediate structure
Ac2O, AcCl
Reflux, 3 h, 79%
intermediate structure
  1. KNH2
  2. NH4Cl
Et2O, NH3
-33 °C, 2 h
intermediate structure
LiAlH4
Et2O
RT, 2 h, 6% (2 steps)
intermediate structure
Ph3CCl
Pyr
100 °C, 4 h
"No yield reported."
intermediate structure
Cyclohexanone, Al(Oi-Pr)3
PhMe
100 °C, 30 min
See the Oppenauer Oxidation
"No yield reported."
intermediate structure
HCl
CHCl3
0 °C to RT, 30 min, 29%
"Second relay molecule."
intermediate structure
BzCl
Pyr
RT
"No yield reported."
intermediate structure
  1. Ph3CNa
  2. CO2
Et2O, PhH
RT
intermediate structure
CH2N2
Et2O
RT, 30 min, 16% (2 steps)
"Also isolated was a regioisomer (36% yield)"
intermediate structure
SiO2, Zn, BrCH2CO2Me
Et2O, PhH
Reflux, 16 h
See the Reformatsky Reaction
intermediate structure
NaOH
H2O, MeOH
Reflux, 27 h, 19% (2 steps)
intermediate structure
PtO2, H2
AcOH
RT, 76-80%
intermediate structure
CH2N2
Et2O, MeOH
RT, 100%
intermediate structure
Ac2O
Pyr
RT, 24 h, 87%
intermediate structure
POCl3
Pyr
0 °C to Reflux, 90 min
intermediate structure
H2, PtO2
AcOH
RT, 20 h
intermediate structure
HCl
MeOH
RT to Reflux, ON
intermediate structure
BzCl
Pyr
RT, 60 min, 10% (4 steps)
"Third relay molecule"
intermediate structure
K2CO3
H2O, MeOH
100 °C, 24 h, 95%
intermediate structure
Ac2O
Pyr
Reflux, 80%
intermediate structure
(COCl)2
PhH
intermediate structure
CH2N2
Et2O, Petroleum ether
-5 °C, ON
intermediate structure
AgNO3, NH3
EtOH, H2O
50 °C, 2.5 h
See the Wolff Rearrangement
intermediate structure
KOH
MeOH
Reflux, 16 h
intermediate structure
Ac2O
AcOH
Reflux, 6 h
intermediate structure
15 mmHg
250-260 °C, 15% (6 steps)
"Fourth relay molecule"
intermediate structure
"No conditions reported."
intermediate structure
CrO3
AcOH
RT, 24 h, 84%
See the Jones Oxidation
"See: Z. Physiol. Chem. 1935, 234, 218."
intermediate structure
Br2, HBr
AcOH, H2O
RT, 68-71%
"See: J. Org. Chem. 1948, 13, 697."
intermediate structure
NaI
Acetone
Reflux
See the Finkelstein Reaction
"See: J. Am. Chem. Soc. 1950, 72, 4077."
intermediate structure
CrCl2
Acetone, H2O
RT, 30 min, 50-60% (2 steps)
"Fifth relay molecule. See: J. Am. Chem. Soc. 1950, 72, 4077."
intermediate structure
Ac2O, AcCl
Reflux, 3 h, 79%
intermediate structure
  1. KNH2
  2. NH4Cl
Et2O, NH3
-33 °C, 2 h
intermediate structure
LiAlH4
Et2O
RT, 5 h, 2.8% (2 steps)
intermediate structure
Ph3CCl
Pyr
100 °C, 6 h, 1.6%
intermediate structure
Al(Oi-Pr)3, Cyclohexanone
PhMe
Reflux, 3 h, 48%
See the Oppenauer Oxidation
intermediate structure
HCl
CHCl3
0 °C to RT, 30 min, 54%
"Sixth relay molecule."
intermediate structure
Ac2O
Pyr
RT, ON, 84%
"See: J. Org. Chem. 1939, 4, 506."
intermediate structure
KCN
AcOH, EtOH
RT, 30 min, 82%
"See: Chem. Ber. 1938, 71, 1487."
intermediate structure
POCl3
Pyr
RT, 10 min, 58%
"See: Chem. Ber. 1938, 71, 1487."
intermediate structure
MeMgBr
Et2O
Reflux, 46 h, 75%
See the Grignard Reaction
"See: Chem. Ber. 1939, 72, 182."
intermediate structure
Ni (Raney), NaOH, H2
EtOH, H2O
RT, 86%
"See: Chem. Ber. 1939, 72, 182."
intermediate structure
Ac2O
Pyr
RT, 93%
"See: J. Org. Chem. 1939, 4, 506."
intermediate structure
H2, PtO2
AcOH
RT, 22 h
"see: Helv. Chim. Acta 1946, 29, 468."
intermediate structure
CrO3
AcOH
RT, 24 h, 86% (2 steps)
See the Jones Oxidation
"See: Helv. Chim. Acta 1946, 29, 468."
intermediate structure + intermediate structure
PhOMe
Reflux, 3 h
See the Grignard Reaction
intermediate structure
Ac2O
Reflux, 30 min
intermediate structure
H2, PtO2, HClO4
AcOH
RT, 15 min, 4.8% (3 steps)
intermediate structure
Report an error in this part
Remaining...
(6 steps)
"See: Org. Synth. 1937, 17, 43; Ber. 1935, 68, 2091; Helv. Chim. Acta 1938, 21, 866; J. Chem. Soc. 1950, 2325; J. Am. Chem. Soc., 1952, 74, 4223."
intermediate structure