Synthesis of Mevinolin

Structure of Mevinolin

C24H36O5

Principal investigator	Derrick L. J. Clive
Publication year	1990
Synthesis type	Total
Number of steps	43 (5 parts)
References	J. Am. Chem. Soc. 1990, 112, 3018.

Part 1 of 5

intermediate structure

i-Pr2NLi, AllylBr

THF

-78 °C to RT, 4 h, 74%

intermediate structure

O3
Ph3P

CH2Cl2

-78 °C to RT, 4 h, 96%

intermediate structure

TsOH, (CH2OH)2

4A MS, Soxhlet

PhH

Reflux, 4.5 h, 87%

intermediate structure

LiAlH4

THF

0 °C to RT, 45 min, 96%

intermediate structure

Et3N, DMSO, (COCl)2

CH2Cl2

-78 °C to RT, 110 min, 90%

See the Swern Oxidation

intermediate structure

Ph3P+CH3 Br-, n-BuLi

-15 to 0 °C, 95 min, 72%

See the Wittig Reaction

intermediate structure

H2O, HCl

Et2O

RT, 23 h, 69%

intermediate structure

Report an error in this part

Part 2 of 5

intermediate structure

BH3.Me2S, B(OMe)3

THF

-5 °C to RT, 51 h, 100%

intermediate structure

3-Pentanone, 3,3-Dimethoxypentane, TsOH.H2O

CH2Cl2

RT, ON, 71%

intermediate structure

DMAP, Et3N, TBDPSCl

CH2Cl2

0 °C to RT, 19 h, 96%

intermediate structure

AcOH

H2O

50 °C, 4 h, 84%

intermediate structure

Pyr, MsCl

CH2Cl2

-30 °C to RT, 40 h, 68%

intermediate structure

Me3N+Bn HO-

H2O, MeOH

RT, 30 min, 91%

intermediate structure

VinylLi, CuCN

THF

-60 to 0 °C, 5.5 h, 96%

intermediate structure

n-BuLi
CO2
I2

THF

0 °C to RT, 5 h, 74%

"85:15 at C6. Major isomer shown"

intermediate structure

TsOH.H2O

Acetone

RT, 91 h

intermediate structure

Et3N, DMAP, TBDPSCl

CH2Cl2

0 °C to RT, 2 h, 67% (2 steps)

intermediate structure

Report an error in this part

Part 3 of 5

intermediate structure

n-BuLi
Crotonyl chloride

THF

-78 °C, 30 min, 79%

intermediate structure

1,3-Butadiene, Et2AlCl

CH2Cl2

-78 to -7 °C, 16 h, 56%

See the Diels-Alder Reaction

intermediate structure

LiOBn

THF

0 °C, 5.5 h, 87%

intermediate structure

LiOMe

CH2Cl2, MeOH

Reflux, 46.5 h, 87%

intermediate structure

i-Pr2NLi
AcOH

THF

-78 °C to RT, 2 h, 59%

"90% BRSM"

intermediate structure

LiAlH4

THF

0 °C to reflux, 15 h, 99%

intermediate structure

TsCl, Pyr, DMAP

CH2Cl2

RT, 24 h, 90%

intermediate structure

NaCN

DMSO

75 °C, 10 h, 92%

intermediate structure

NaOH

H2O

Reflux, 24 h, 92%

intermediate structure

NaI, 18-Crown-6, mCPBA

CH2Cl2

-10 °C, 75 min, 91%

intermediate structure

DBU

PhMe

Reflux, 2 h, 79%

intermediate structure

Report an error in this part

Part 4 of 5

intermediate structure

+

intermediate structure

i-Pr2NLi

HMPA, THF

-78 °C to RT, ON, 35%

"77% BRSM"

intermediate structure

i-Bu2AlH

CH2Cl2

-78 °C, 95 min, 90%

intermediate structure

NaOAc, MnO2

CHCl3

RT, 74.5 h, 78%

intermediate structure

(Ph3P)3RhCl

PhMe, PhCN

Reflux, 2.5 h, 50%

intermediate structure

Report an error in this part

Part 5 of 5

intermediate structure

+

intermediate structure

i-Pr2NLi

Et2O

-78 °C, 75 min, 78%

See the Aldol Addition

intermediate structure

DMAP, TESCl, i-Pr2NH

Et2O

0 °C to RT, 24.5 h, 69%

"85% BRSM"

intermediate structure

O3
Ph3P

CH2Cl2

-78 °C to RT, 3 h, 59%

"85% BRSM"

intermediate structure

TiCl3, C8K

DME

RT to reflux, 20 h, 86%

See the McMurry Reaction

intermediate structure

n-Bu4N+ F-

THF

RT, 22 h

intermediate structure

TBDPSCl, Et3N, DMAP

CH2Cl2

0 °C to RT, 24 h, 95% (2 steps)

intermediate structure

Special reagent

DMAP, Et3N

CH2Cl2

RT, 72 h, 80%

"91% BRSM"

intermediate structure

n-Bu4N+ F-

THF

RT, 3 h, 95%

intermediate structure

(COCl)2, DMSO, Et3N

CH2Cl2

-78 °C to RT, 50 min, 97%

See the Swern Oxidation

intermediate structure

HCl

H2O, THF

RT, 4 h, 97%

intermediate structure

Ag2CO3/Celite

PhMe

85-95 °C, 1 h, 77%

intermediate structure

Report an error in this part