Synthesis of Ingenol

C20H28O5
Principal investigator | John L. Wood |
---|---|
Publication year | 2004 |
Synthesis type | Total |
Number of steps | 33 (linear) |
References |
Part 1 of 1
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TsOH,
(CH2OH)2
Dean-Stark
PhH
Reflux, 12 h, 35% (2 steps)
"The product was separated from the resulting four diastereoisomers."

LiAlH4
Et2O
RT, 2 h

HCl
Acetone
RT, 30 min, 95% (2 steps)

DMAP,
Ac2O
Pyr
RT, 30 min, 96%

DBU
PhH
Reflux, 10 h, 88%


BF3.OEt2
PhMe
-78 °C, 85 min, 59%
See the Diels-Alder Reaction
"The product was separated from the resulting three diastereoisomers."



NaIO4
H2O, MeOH, THF
RT, 60 min

Pyr.TsOH,
(CH2OH)2
Dean-Stark
PhH
Reflux, 4 h, 73% (3 steps)


KH
THF
Reflux, ON, 98%


HCl
H2O, THF
Reflux, 3 h

NaBH4
EtOH, THF
0 °C, 15 min, 77% (2 steps)


KOt-Bu
DMSO
RT, ON, 94% (2 steps)

t-BuOOH,
SeO2
AcOH, CH2Cl2
0 °C to RT, 2 h, 49%
"The yield was 70 % brsm."


RhCl3
Sealed tube
EtOH, H2O
115 °C, 35 min, 74%

P(OMe)3,
O2,
KOt-Bu
t-BuOH, THF
-40 °C, 45 min, 94%

VO(acac)2,
t-BuOOH
PhH
10 °C to RT, 10 h, 73%

TMSOTf,
Et3N
CH2Cl2
-10 to -5 °C, 60 min, 72%

NaBH4
MeOH
RT, 5 h

Pyr.TsOH,
2,2-Dimethoxypropane
CH2Cl2
Reflux, 30 min, 86% (2 steps)

DDQ
CH2Cl2
RT, 18 h, 90%

MsCl,
Et3N
CH2Cl2
-78 °C, 45 min, 96%

Li2CO3,
PhSH
DMF
55 °C, 5 h, 76%

(NH4)6Mo7O24.4H2O,
H2O2
EtOH, H2O
RT, 6 h, 97%

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."

Na2HPO4,
Na(Hg)
MeOH
-20 to -10 °C, 25 min, 76%

HCl
H2O, THF
RT, 5 h, 92%

SiO2,
SeO2
THF
80 °C, 2 h, 40%
"The yield was 89 % brsm."
