Synthesis of Taxol
C47H51NO14
| Principal investigator | Paul A. Wender |
|---|---|
| Publication year | 1997 |
| Synthesis type | Formal |
| Number of steps | 38 (linear) |
| References |
Part 1 of 1
KOt-Bu,
PrenylBr
DME
-78 °C to RT, 4 h, 41%
"The yield was 82 % brsm."
- O3
- Thiourea
CH2Cl2, MeOH
5 h, 85%
hν
MeOH
0 °C, 3 h, 85%
- Ethyl propynoate , i-Pr2NLi
- TMSCl
THF
-78 to 0 °C, 89%
(Ph3P)3RuCl2,
NMO
Acetone
RT, 60 min, 95%
TMS2NK
THF
-78 to -20 °C, 2 h, 56%
"97.5 % yield at 57 % conversion."
LiAlH4
Et2O
-78 to 0 °C, 2.5 h, 74%
- Imidazole , TBSCl
- 2-Methoxypropene , Pyr.TsOH
CH2Cl2
0 °C to RT, 8 h, 91%
2,6-Lutidine,
TIPSOTf,
DABCO
CH2Cl2
-78 °C to Reflux, 14 h, 85% (2 steps)
See the Grob Fragmentation
KOt-Bu,
O2,
P(OEt)3
THF
-40 °C, 10 min, 74%
NaBH4
MeOH
RT, 90 min, 91%
H2
1 atm
CH2Cl2
RT, 30 min, 92%
Triphosgene,
TMSCl
Pyr
-78 °C to RT, 2 h, 95%
HCrO3Cl.Pyr
4 Å MS
CH2Cl2
RT, 2 h, 100%
NaI,
HCl
Dioxane , H2O
RT, 18 h, 85%
"94 % yield based on 90 % conversion."
TESCl,
Pyr
CH2Cl2
-78 to -20 °C, 10 h, 92%
- Dess-Martin Periodinane , NaHCO3
- H2CN+Me2 I- , Et3N
CH2Cl2
RT, ON, 97%
See the Dess-Martin Oxidation
See the Mannich Reaction
i-Pr2NEt,
BnOCH2Cl
Sealed tube
CH2Cl2
60 °C, 72 h
NH4F
MeOH
RT, 12 h, 93% (2 steps)
- PhLi
- Ac2O , DMAP , Pyr
THF
-78 °C to RT, 2.5 h, 79%
CH2Cl2
80 min, 50%
"80 % yield based on 63 % conversion."
- O3
- P(OEt)3
CH2Cl2
-78 °C to RT, 86%
HCl,
NaI
Acetone, H2O
RT, 21 h, 65%
"97 % yield based on 67 % conversion."
MsCl,
DMAP
CH2Cl2, Pyr
0 °C, 3 h, 83%
Pyr,
OsO4
THF
RT, 23 h, 71%
"76 % yield based on 94 % conversion."
Triphosgene,
Pyr
CH2Cl2
0 °C, 30 min, 92%
KCN
EtOH
0 °C, 3 h, 68%
"76 % yield based on 89 % conversion."
i-Pr2NEt
PhMe
Reflux, 9 h, 79%
"95 % yield based on 83 % conversion."
DMAP,
Ac2O
CH2Cl2
RT, ON, 89%
TASF
THF
0 °C, 5 min, 96%
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."
Remaining...
54% (3 steps)
"See : Chem. Eur. J. 1999, 5, 121; Nature 1994, 367, 630."