Synthesis of Ingenol

C20H28O5
Principal investigator | Isao Kuwajima |
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Publication year | 2003 |
Synthesis type | Total |
Number of steps | 46 (linear) |
References |
Part 1 of 1
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NBS
DMSO, H2O
10 °C, 2 h, 32%
See the Prins Reaction
"Also isolated was the C2-epimer which was reverted to the starting material with zinc/ammonium chloride (52 % yield)."

Imidazole,
TESCl
DMF
0 °C, 60 min, 99%


DBU,
(CF3CO)2O
PhH, Pyr
-23 to 0 °C, 35 min, 95%


- AlMe3
- i-Pr2NLi
- HCl , H2O
THF
-78 °C to RT, 30 h, 66%

TIPSCl,
DMAP
DMF
RT, 16 h, 100%

LiAlH4
THF
0 to 50 °C, 4 h, 84%
"The yield was 92 % brsm."





Et3N,
DMAP,
Ac2O
CH2Cl2
0 °C to RT, 30 min, 99%

Co2(CO)8
CH2Cl2
RT, 60 min, 95%


Li
NH3
-78 °C, 60 min, 67% (2 steps)

CHBr3,
Et3NBn+ Cl-,
NaOH
CH2Cl2, EtOH, H2O
0 °C, 5 h, 32%
"The yield was 71% brsm."


Ti(Oi-Pr)4,
t-BuOOH
4 Å MS
CH2Cl2
-20 to 0 °C, 60 min





- i-Bu2AlH
- MeI , THF
CH2Cl2
-78 °C to RT, 30 min, 98% (2 steps)

NaBH4
EtOAc
-78 to 0 °C, 30 min, 95%

i-Bu2AlH
CH2Cl2
-78 °C, 2 h

- Tf2O , 2,6-Lutidine
- DBU
CH2Cl2
-78 °C to RT, 90 min, 83% (2 steps)

n-Bu4N+ F-
THF
RT, 30 min

H2Cr2O7.2Pyr
4 Å MS
CH2Cl2
RT, 2 h, 97% (2 steps)


DMF
120 °C, 3 h, 78%
"The yield was 86% brsm."


TESCl,
Imidazole
DMF
0 °C, 30 min, 99% (2 steps)

OsO4
Et2O, Pyr
RT, 48 h, 59%

CDI
PhH
RT, 60 min, 76%
"Also isolated was the desired regioisomer (18 % yield, see next step)."

DMAP
PhMe
100 °C, 2 h, 27%
"The yield was 99 % brsm."


Camphorsulfonic acid
RT, 3 h, 92%

SOCl2
Pyr
RT, 30 min

Ac2O
H2O
60 °C, 3 h, 96% (2 steps)


TESOTf,
2,6-Lutidine
CH2Cl2
0 °C, 60 min

- TMSCl , i-Pr2NLi
- Et3N
THF
-78 °C, 2 h

NBS
CH2Cl2
0 °C, 30 min

HF
H2O, MeCN
RT, 30 min


CH2I2,
MeLi
THF
-78 °C, 60 min, 39% (5 steps)

Zn,
NH4Cl
H2O, THF
RT, 30 min, 91%

KOH
MeOH
RT, 30 min, 89%
