Synthesis of Taxol

Structure of Taxol

C47H51NO14

Principal investigatorPaul A. Wender
Publication year1997
Synthesis typeFormal
Number of steps 38 (linear)
References
Part 1 of 1
intermediate structure
KOt-Bu, PrenylBr
DME
-78 °C to RT, 4 h, 41%
"The yield was 82 % brsm."
intermediate structure
  1. O3
  2. Thiourea
CH2Cl2, MeOH
5 h, 85%
intermediate structure
MeOH
0 °C, 3 h, 85%
intermediate structure
  1. Ethyl propynoate
  2. i-Pr2NLi
  3. TMSCl
THF
-78 to 0 °C, , 89%
intermediate structure
MeLi, CuI
Et2O
-78 °C to RT, ON, 97%
See the Aldol Addition
intermediate structure
(Ph3P)3RuCl2, NMO
Acetone
RT, 60 min, 95%
intermediate structure
TMS2NK
THF
-78 to -20 °C, 2 h, 56%
"97.5 % yield at 57 % conversion."
intermediate structure
LiAlH4
Et2O
-78 to 0 °C, 2.5 h, 74%
intermediate structure
  1. TBSCl
  2. Imidazole
  3. Pyr.TsOH
  4. 2-Methoxypropene
CH2Cl2
0 °C to RT, 8 h, 91%
intermediate structure
mCPBA, Na2CO3
CH2Cl2
-78 to -15 °C, 14 h
intermediate structure
DABCO, TIPSOTf, 2,6-Lutidine
CH2Cl2
-78 °C to Reflux, 14 h, 85% (2 steps)
intermediate structure
O2, P(OEt)3, KOt-Bu
THF
-40 °C, 10 min, 74%
intermediate structure
NaBH4
MeOH
RT, 90 min, 91%
intermediate structure
H2
CH2Cl2
RT, 30 min, 92%
intermediate structure
TMSCl, Triphosgene
Pyr
-78 °C to RT, 2 h, 95%
intermediate structure
HCrO3Cl.Pyr
CH2Cl2
RT, 2 h, 100%
intermediate structure
Ph3P+CH2OMe Cl-, TMS2NK
THF
-78 °C to RT, 85 min, 91%
See the Wittig Reaction
intermediate structure
HCl, NaI
Dioxane , H2O
RT, 18 h, 85%
"94 % yield based on 90 % conversion."
intermediate structure
TESCl, Pyr
CH2Cl2
-78 to -20 °C, 10 h, 92%
intermediate structure
  1. Dess-Martin Periodinane
  2. NaHCO3
  3. H2CN+Me2 I-
  4. Et3N
CH2Cl2
RT, ON, 97%
intermediate structure
AllylMgBr, ZnCl2
THF
-78 °C, 17 min, 89%
intermediate structure
BnOCH2Cl, i-Pr2NEt
CH2Cl2
60 °C, 72 h
intermediate structure
NH4F
MeOH
RT, 12 h, 93% (2 steps)
intermediate structure
  1. PhLi
  2. Ac2O
  3. Pyr
  4. DMAP
THF
-78 °C to RT, 2.5 h, 79%
intermediate structure
CH2Cl2
80 min, 50%
"80 % yield based on 63 % conversion."
intermediate structure
  1. O3
  2. P(OEt)3
CH2Cl2
-78 °C to RT, , 86%
intermediate structure
ClCO2CH2CCl3, DMAP
CH2Cl2
RT, 42 h, 62%
See the Aldol Addition
intermediate structure
HCl, NaI
Acetone, H2O
RT, 21 h, 65%
"97 % yield based on 67 % conversion."
intermediate structure
MsCl, DMAP
CH2Cl2, Pyr
0 °C, 3 h, 83%
intermediate structure
LiBr
Acetone
RT, 72 h, 73%
"79 % yield based on 94 % conversion."
intermediate structure
OsO4, Pyr
THF
RT, 23 h, 71%
"76 % yield based on 94 % conversion."
intermediate structure
Triphosgene, Pyr
CH2Cl2
0 °C, 30 min, 92%
intermediate structure
KCN
EtOH
0 °C, 3 h, 68%
"76 % yield based on 89 % conversion."
intermediate structure
i-Pr2NEt
PhMe
Reflux, 9 h, 79%
"95 % yield based on 83 % conversion."
intermediate structure
Ac2O, DMAP
CH2Cl2
RT, ON, 89%
intermediate structure
TASF
THF
0 °C, 5 min, 96%
intermediate structure
PhLi
THF
-78 °C to RT, 15 min, 58%
"Also isolated was the C10-alcohol (30 % yield) which can be acetylated to the desired product."
intermediate structure
Remaining...
54% (3 steps)
"See : Chem. Eur. J. 1999, 5, 121; Nature 1994, 367, 630."
intermediate structure