Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigatorSamuel J. Danishefsky
Publication year1996
Synthesis typeFormal
Number of steps 52 (2 parts)
References
Part 1 of 2
intermediate structure
NH2NH2, Et3N
EtOH
RT, 90 min, 72%
intermediate structure
I2, DBN
THF
RT, 45 min, 52%
intermediate structure
I2, DBN
THF
0 °C to RT, 8.5 h, 89%
intermediate structure
TMSCN, KCN, 18-Crown-6
CH2Cl2
0 °C to RT, 8 h, 89%
intermediate structure
Part 2 of 2
intermediate structure
NaBH4
EtOH
0 °C, , 97%
intermediate structure
Ac2O, DMAP
CH2Cl2, Pyr
0 °C, , 99%
intermediate structure
(CH2OH)2, Naphthalenesulfonic Acid
PhH
Reflux, , 70%
intermediate structure
NaOMe
MeOH, THF
98%
intermediate structure
TBSOTf, 2,6-Lutidine
CH2Cl2
0 °C, , 97%
intermediate structure
BH3.THF, H2O2, NaOH
THF, H2O
0 °C to RT, 17 h
intermediate structure
H2Cr2O7.2Pyr
CH2Cl2
0 °C to RT, 10.5 h
intermediate structure
NaOMe
MeOH
RT, 10 h, 62% (3 steps)
intermediate structure
Me3S+ I-, TMS2NK
THF
0 °C, 2.5 h, 99%
intermediate structure
Al(Oi-Pr)3
PhMe
Reflux, 38 h, 99%
intermediate structure
OsO4, NMO
Acetone, i-PrOH, H2O
RT, 15 h, 66%
intermediate structure
TMSCl, Tf2O, Pyr
CH2Cl2, Ethylene Glycol
-78 °C to Reflux, , 69%
intermediate structure
BnBr, NaH, n-Bu4N+ I-
THF
0 °C to RT, 4.5 h, 98%
intermediate structure
TsOH
Acetone, H2O
Reflux, 2.5 h, 84%
intermediate structure
TMSOTf, Et3N
CH2Cl2
-78 °C, 4 h
intermediate structure
DMDO
CH2Cl2
0 °C, 10 min
intermediate structure
Camphorsulfonic acid
Acetone
RT, 30 min, 89% (3 steps)
intermediate structure
Pb(OAc)4
PhH, MeOH
0 °C, 10 min, 97%
intermediate structure
CTPS
MeOH
Reflux, 10 h, 97%
intermediate structure
LiAlH4
THF
0 °C, 60 min, 100%
intermediate structure
o-NO2PhSeCN, n-Bu3P
THF
RT, 15 min, 88%
intermediate structure
H2O2
THF
RT, 12 h, 90%
intermediate structure
  1. O3
  2. Ph3P
CH2Cl2
-78 °C, , 79%
intermediate structure + intermediate structure
t-BuLi
THF
-78 °C, 55 min, 93%
intermediate structure
n-Bu4N+ F-
THF
-78 °C, 15 min, 80%
intermediate structure
mCPBA, NaHCO3
CH2Cl2
RT, 11 h, 80%
intermediate structure
H2, Pd/C
EtOH
-5 °C, , 65%
intermediate structure
CDI, NaH
DMF
RT, 20 min, 81%
intermediate structure
Li(s-Bu)3BH
THF
-78 °C, 75 min, 93%
intermediate structure
  1. TMS2NK
  2. PhNTf2
THF
-78 °C, 10 min, 98%
intermediate structure
Pyr.TsOH
Acetone, H2O
75 °C, 9 h, 96%
intermediate structure
Ph3P=CH2
THF
-78 to 0 °C, 25 min, 77%
See the Wittig Reaction
intermediate structure
Pd(PPh3)4, K2CO3
MeCN
90 °C, , 46%
See the Heck Coupling
intermediate structure
n-Bu4N+ F-
THF
RT, 8 h, 92%
intermediate structure
TESOTf, Et3N
CH2Cl2
-78 °C, 30 min, 92%
intermediate structure
mCPBA, NaHCO3
CH2Cl2
RT, 10.5 h, 45%
intermediate structure
H2, Pd/C
EtOH
RT, 10 h, 82%
intermediate structure
Ac2O, DMAP
Pyr
RT, 16 h, 66%
intermediate structure
PhLi
THF
-78 °C, 2 min, 93%
intermediate structure
OsO4
Pyr
105 °C, 24 h
intermediate structure
Pb(OAc)4
PhH, MeOH
0 °C, 5 min, 61% (2 steps)
intermediate structure
SmI2, Ac2O
THF
-78 °C, 10 min, 92%
intermediate structure
(PhSeO)2O, KOt-Bu
THF
-78 to 0 °C, 90 min
intermediate structure
KOt-Bu
THF
-78 °C, 10 min, 81% (2 steps)
intermediate structure
Ac2O, DMAP
Pyr
RT, 16 h, 76%
intermediate structure
HCrO3Cl.Pyr, NaOAc
PhH
Reflux, 60 min, 64%
intermediate structure
NaBH4
MeOH
RT, 2 h, 79%
intermediate structure
Remaining...
63% (2 steps)
"See : Nature 1994, 367, 630."
intermediate structure