Synthesis of Taxol

C47H51NO14
Principal investigator | Kyriacos C. Nicolaou |
---|---|
Publication year | 1994 |
Synthesis type | Total |
Number of steps | 40 (3 parts) |
References |
Part 1 of 3
+


KOH
t-BuOH
65 °C, 3 h, 50%

TBSCl
CH2Cl2
RT, 60 min, 100%


THF
RT, 3 h, 80%

Part 2 of 3
+



TBSOTf,
DMAP,
2,6-Lutidine
CH2Cl2
0 °C, 4 h, 95%

LiAlH4
Et2O
0 °C, 60 min, 94%

Camphorsulfonic acid
MeOH
RT, 60 min, 90%

TBDPSCl,
Imidazole
DMF
RT, 6 h, 92%


LiAlH4
Et2O
RT, 12 h, 80%

2,2-Dimethoxypropane,
Camphorsulfonic acid
CH2Cl2
RT, 7 h, 82%


Part 3 of 3
+
+
+



VO(acac)2,
t-BuOOH
4 Å MS
PhH
RT, 12 h, 87%

LiAlH4
Et2O
RT, 7 h, 76%

KH,
Phosgene
Et2O, HMPA
RT, 2 h, 48%

n-Bu4N+ F-
THF
RT, 7 h, 80%




43%
"Also isolated was the correponding diastereoisomer (43% yield)."

K2CO3
MeOH
90%

DMAP,
Ac2O
CH2Cl2
RT, 2 h, 95%


- BH3.THF
- H2O , H2O2
THF
0 °C, 2.5 h, 55%

HCl
H2O, MeOH
RT, 5 h, 80%

DMAP,
Ac2O
CH2Cl2
RT, 30 min, 95%

Pd/C,
H2
EtOAc
RT, 30 min, 97%

TESCl
Pyr
RT, 12 h, 85%

K2CO3
MeOH
0 °C, 15 min, 95%

TMSCl,
Pyr
CH2Cl2
0 °C, 15 min, 96%

Tf2O,
i-Pr2NEt
CH2Cl2
RT, 30 min, 70%

Camphorsulfonic acid
MeOH
10 min

SiO2
CH2Cl2
4 h, 60% (2 steps)

DMAP,
Ac2O
CH2Cl2
RT, 4 h, 94%

PhLi
THF
-78 °C, 10 min, 80%

Celite,
HCrO3Cl.Pyr,
NaOAc
PhH
Reflux, 60 min, 75%

NaBH4
MeOH
RT, 5 h, 83%


TMS2NNa
THF
0 °C, 78%
"87 % yield at 90 % conversion."

Pyr.HF
THF
RT, 90 min, 80%
