Synthesis of Cyanocobalamin
C63H89CoN14O14P
Principal investigator | Robert B. Woodward |
---|---|
Publication year | 1973 |
Synthesis type | Formal |
Number of steps | 72 (7 parts) |
References |
Part 1 of 7
+
+
SnCl4
PhH
RT, 73%
See the Diels-Alder Reaction
"The enantiomers were resolved with (+)- and (-)-phenylethylamine."
CrO3,
H2SO4
Acetone
RT, 75%
SOCl2
77 °C
CH2N2
Dioxane , Et2O
RT
NH3
MeOH
RT, 55%
P2S5
THF
RT, 85%
Part 2 of 7
CH2N2,
NaOMe
Et2O, MeOH
92%
H2S
CF3CO2H
RT, 78%
(Ph3P)3RhCl
PhMe
110 °C, 30%
Part 3 of 7
+
HCl,
Bz2O
CH2Cl2
RT
P2S5,
4-Methylpyridine
Xylene(s)
130 °C, 84%
Part 4 of 7
+
MeMgI,
Propargyl bromide
""the diastereomeric ureas resulting from the combination of the racemic tricyclic ketone with optically active alpha-phenylethylisocyanate are very readily separable""
""and are readily re-converted to the parent active tricyclic ketones when pyrolyzed""
Part 5 of 7
+
"No experimental details were reported for this whole part."
LiAlH4
CrO3
Part 6 of 7
+
(CH2OH)2,
TsOH
PhH
Et3O+ BF4-
MeOH
PhMe
Reflux
90%
""When subjected to acid treatment under carefully controlled condition""
""further treated with acid""
NH2OH
NaNO2
AcOH
HIO4,
O3
MeOH
CH2N2
Et2O
MsCl,
Et3N
HIO4,
O3
EtOAc, H2O
CH2N2
Et2O
Polystyrenesulfonic acid
MeOH
170 °C
See the Beckmann Rearrangement
"Also isolated was the C3-epimer which was equilibrated to the desired product."
HCl,
PhSH
MeOH
O3
NH3
NaBH4
Ms2O
Part 7 of 7
+
KOt-Bu
100%
P2S5,
4-Methylpyridine
PhMe
Me2NH
ZnCl2
I2
MeOH
""it was a relatively easy matter to remove the zinc by treatment with acid""
CoCl2
THF
NaCN
I2
AcOH
PhSH
Ni (Raney)
CH2N2
Et2O
H2SO4
H2O
60 min
"Also isolated was the C13-epimer in an unfavorable 28:72 ratio."
N2O4,
NaOAc
CCl4
0 °C, 60 min, 70-80%
NH3,
NH4Cl
Ethylene Glycol
75 °C, 10 h, 100%
Remaining...
(1 step)
"See: Helv. Chim. Acta 1960 , 43, 704."