Synthesis of Taxol

C47H51NO14
Principal investigator | Samuel J. Danishefsky |
---|---|
Publication year | 1996 |
Synthesis type | Formal |
Number of steps | 52 (2 parts) |
References |
Part 1 of 2

Et3N,
NH2NH2
EtOH
RT, 90 min, 72%


DBN,
I2
THF
0 °C to RT, 8.5 h, 89%

KCN,
18-Crown-6,
TMSCN
CH2Cl2
0 °C to RT, 8 h, 89%

Part 2 of 2
+

NaBH4
EtOH
0 °C, 97%

DMAP,
Ac2O
CH2Cl2, Pyr
0 °C, 99%

Naphthalenesulfonic Acid,
(CH2OH)2
Dean-Stark
PhH
Reflux, 70%

NaOMe
MeOH, THF
98%

TBSOTf,
2,6-Lutidine
CH2Cl2
0 °C, 97%

NaOH,
H2O2,
BH3.THF
H2O, THF
0 °C to RT, 17 h

H2Cr2O7.2Pyr
4 Å MS
CH2Cl2
0 °C to RT, 10.5 h

NaOMe
MeOH
RT, 10 h, 62% (3 steps)


Al(Oi-Pr)3
PhMe
Reflux, 38 h, 99%


Pyr,
Tf2O,
TMSCl
CH2Cl2, Ethylene Glycol
-78 °C to Reflux, 69%


TsOH
Acetone, H2O
Reflux, 2.5 h, 84%

TMSOTf,
Et3N
CH2Cl2
-78 °C, 4 h

DMDO
CH2Cl2
0 °C, 10 min



CTPS
MeOH
Reflux, 10 h, 97%

LiAlH4
THF
0 °C, 60 min, 100%

o-NO2PhSeCN,
n-Bu3P
THF
RT, 15 min, 88%


- O3
- Ph3P
CH2Cl2
-78 °C, 79%


t-BuLi
THF
-78 °C, 55 min, 93%

n-Bu4N+ F-
THF
-78 °C, 15 min, 80%


Pd/C,
H2
1 atm
EtOH
-5 °C, 65%

CDI,
NaH
DMF
RT, 20 min, 81%

Li(s-Bu)3BH
THF
-78 °C, 75 min, 93%

- TMS2NK
- PhNTf2
THF
-78 °C, 10 min, 98%

Pyr.TsOH
Acetone, H2O
75 °C, 9 h, 96%



n-Bu4N+ F-
THF
RT, 8 h, 92%

TESOTf,
Et3N
CH2Cl2
-78 °C, 30 min, 92%


H2,
Pd/C
1 atm
EtOH
RT, 10 h, 82%

DMAP,
Ac2O
Pyr
RT, 16 h, 66%

PhLi
THF
-78 °C, 2 min, 93%

OsO4
Pyr
105 °C, 24 h


SmI2,
Ac2O
THF
-78 °C, 10 min, 92%

(PhSeO)2O,
KOt-Bu
THF
-78 to 0 °C, 90 min


DMAP,
Ac2O
Pyr
RT, 16 h, 76%

HCrO3Cl.Pyr,
NaOAc
PhH
Reflux, 60 min, 64%

NaBH4
MeOH
RT, 2 h, 79%

Remaining...
63% (2 steps)
"See : Nature 1994, 367, 630."
