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%