Synthesis of Mevinolin

C24H36O5
Principal investigator | Derrick L. J. Clive |
---|---|
Publication year | 1990 |
Synthesis type | Total |
Number of steps | 43 (5 parts) |
References |
Part 1 of 5

i-Pr2NLi,
AllylBr
THF
-78 °C to RT, 4 h, 74%

- O3
- Ph3P
CH2Cl2
-78 °C to RT, 4 h, 96%

TsOH,
(CH2OH)2
4A MS, Soxhlet
PhH
Reflux, 4.5 h, 87%

LiAlH4
THF
0 °C to RT, 45 min, 96%



H2O,
HCl
Et2O
RT, 23 h, 69%

Part 2 of 5

BH3.Me2S,
B(OMe)3
THF
-5 °C to RT, 51 h, 100%

3-Pentanone,
3,3-Dimethoxypentane,
TsOH.H2O
CH2Cl2
RT, ON, 71%

DMAP,
Et3N,
TBDPSCl
CH2Cl2
0 °C to RT, 19 h, 96%

AcOH
H2O
50 °C, 4 h, 84%

Pyr,
MsCl
CH2Cl2
-30 °C to RT, 40 h, 68%

Me3N+Bn HO-
H2O, MeOH
RT, 30 min, 91%

VinylLi,
CuCN
THF
-60 to 0 °C, 5.5 h, 96%

- n-BuLi
- CO2
- I2
THF
0 °C to RT, 5 h, 74%
"85:15 at C6. Major isomer shown"

TsOH.H2O
Acetone
RT, 91 h

Et3N,
DMAP,
TBDPSCl
CH2Cl2
0 °C to RT, 2 h, 67% (2 steps)

Part 3 of 5

- n-BuLi
- Crotonyl chloride
THF
-78 °C, 30 min, 79%


LiOBn
THF
0 °C, 5.5 h, 87%

LiOMe
CH2Cl2, MeOH
Reflux, 46.5 h, 87%

- i-Pr2NLi
- AcOH
THF
-78 °C to RT, 2 h, 59%
"90% BRSM"

LiAlH4
THF
0 °C to reflux, 15 h, 99%

TsCl,
Pyr,
DMAP
CH2Cl2
RT, 24 h, 90%

NaCN
DMSO
75 °C, 10 h, 92%

NaOH
H2O
Reflux, 24 h, 92%

NaI,
18-Crown-6,
mCPBA
CH2Cl2
-10 °C, 75 min, 91%

DBU
PhMe
Reflux, 2 h, 79%

Part 4 of 5
+


i-Pr2NLi
HMPA, THF
-78 °C to RT, ON, 35%
"77% BRSM"

i-Bu2AlH
CH2Cl2
-78 °C, 95 min, 90%

NaOAc,
MnO2
CHCl3
RT, 74.5 h, 78%

(Ph3P)3RhCl
PhMe, PhCN
Reflux, 2.5 h, 50%

Part 5 of 5
+



DMAP,
TESCl,
i-Pr2NH
Et2O
0 °C to RT, 24.5 h, 69%
"85% BRSM"

- O3
- Ph3P
CH2Cl2
-78 °C to RT, 3 h, 59%
"85% BRSM"


n-Bu4N+ F-
THF
RT, 22 h

TBDPSCl,
Et3N,
DMAP
CH2Cl2
0 °C to RT, 24 h, 95% (2 steps)


DMAP,
Et3N
CH2Cl2
RT, 72 h, 80%
"91% BRSM"

n-Bu4N+ F-
THF
RT, 3 h, 95%


HCl
H2O, THF
RT, 4 h, 97%

Ag2CO3/Celite
PhMe
85-95 °C, 1 h, 77%
