Synthesis of Ingenol

Structure of Ingenol

C20H28O5

Principal investigatorJohn L. Wood
Publication year2004
Synthesis typeTotal
Number of steps 33 (linear)
References
Part 1 of 1
intermediate structure
CuCN, MeLi
Et2O
-78 °C, 2 h
intermediate structure
(CH2OH)2, TsOH
PhH
Reflux, 12 h, 35% (2 steps)
"The product was separated from the resulting four diastereoisomers."
intermediate structure
LiAlH4
Et2O
RT, 2 h
intermediate structure
HCl
Acetone
RT, 30 min, 95% (2 steps)
intermediate structure
Ac2O, DMAP
Pyr
RT, 30 min, 96%
intermediate structure
DBU
PhH
Reflux, 10 h, 88%
intermediate structure + intermediate structure
BF3.OEt2
PhMe
-78 °C, 85 min, 59%
"The product was separated from the resulting three diastereoisomers."
intermediate structure
C2H4, Grubbs catalyst (2nd gen.)
CH2Cl2
RT, 12 h, 98%
intermediate structure
NMO, OsO4
H2O, THF
RT, 8 h
intermediate structure
NaIO4
H2O, MeOH, THF
RT, 60 min
intermediate structure
(CH2OH)2, Pyr.TsOH
PhH
Reflux, 4 h, 73% (3 steps)
intermediate structure + intermediate structure
KH
THF
Reflux, ON, 98%
intermediate structure
Grubbs-Hoveyda catalyst (2nd gen.)
PhMe
RT, 30 h, 76%
intermediate structure
HCl
H2O, THF
Reflux, 3 h
intermediate structure
NaBH4
EtOH, THF
0 °C, 15 min, 77% (2 steps)
intermediate structure
I2, Imidazole, Ph3P
THF
0 °C, 3 h
See the Appel Reaction
intermediate structure
KOt-Bu
DMSO
RT, ON, 94% (2 steps)
intermediate structure
SeO2, t-BuOOH
AcOH, CH2Cl2
0 °C to RT, 2 h, 49%
"The yield was 70 % brsm."
intermediate structure
Dess-Martin Periodinane
CH2Cl2
-40 to 10 °C, 90 min, 74%
intermediate structure
RhCl3
EtOH, H2O
115 °C, 35 min, 74%
intermediate structure
KOt-Bu, O2, P(OMe)3
t-BuOH, THF
-40 °C, 45 min, 94%
intermediate structure
t-BuOOH, VO(acac)2
PhH
10 °C to RT, 10 h, 73%
intermediate structure
Et3N, TMSOTf
CH2Cl2
-10 to -5 °C, 60 min, 72%
intermediate structure
NaBH4
MeOH
RT, 5 h
intermediate structure
Pyr.TsOH, 2,2-Dimethoxypropane
CH2Cl2
Reflux, 30 min, 86% (2 steps)
intermediate structure
DDQ
CH2Cl2
RT, 18 h, 90%
intermediate structure
Et3N, MsCl
CH2Cl2
-78 °C, 45 min, 96%
intermediate structure
PhSH, Li2CO3
DMF
55 °C, 5 h, 76%
intermediate structure
H2O2, (NH4)6Mo7O24.4H2O
EtOH, H2O
RT, 6 h, 97%
intermediate structure
DBU
PhH
Reflux, 5 h, 47%
"Also isolated was a mixture of E/Z exocyclic sulfones (47 % yield) which could be equilibrated to afford the desired allylic sulfone."
intermediate structure
Na(Hg), Na2HPO4
MeOH
-20 to -10 °C, 25 min, 76%
intermediate structure
HCl
H2O, THF
RT, 5 h, 92%
intermediate structure
SeO2, SiO2
THF
80 °C, 2 h, 40%
"The yield was 89 % brsm."
intermediate structure