Synthesis of Cortistatin A

C30H36N2O3
Principal investigator | Phil S. Baran |
---|---|
Publication year | 2008 |
Synthesis type | Partial |
Number of steps | 19 (linear) |
References |
Part 1 of 1
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- BH3.THF
- NaIO4 , H2O , Acetone
THF
0 °C to RT, 4 h
""Prednisone [...] at $1.20/g possesses 70% of the carbon atoms and the corresponding, enantiopure chirality of [cortistatin A]""

TsOH,
(CH2OH)2
PhMe
Reflux, 60 min, 92% (2 steps)


- NH4OAc , NaBH3CN
- Et3N , HCO2Et
MeOH, THF
RT to 54 °C, 48 h, 73%

n-Bu4N+ OAc-,
Co(acac)2
PhH
90 °C, 24 h, 48%
"The yield was 76 % brsm."

- PhSiH3 , O2 , Co(acac)2
- TsOH
- K2CO3 , MeOH
THF, HC(OMe)3
RT, 14 h, 63%
See the Mukaiyama Hydration
"Three stage, one pot reaction."

PhI(OAc)2,
Br2
hν
CH2Cl2
-30 °C, 10 h

TMSCl,
Imidazole
CH2Cl2
0 °C, 15 min, 57% (2 steps)

LiCl,
DBU
THF
RT, 24 h, 85%


SmI2
THF, DMPU
-72 °C to RT, 35 min

LiBr,
Li2CO3
DMF
60 °C, 60 min, 63% (2 steps)

- AlH3
- MeOH , K2CO3
THF
RT, 13 h

Ac2O,
DMAP,
Et3N
CH2Cl2
RT, 5 h, 89% (2 steps)

2,6-Di-tert-butylpyridine,
MgBr2.OEt2
PhH
78 °C, 90 min

- Pyr.TsOH
- K2CO3
H2O, MEK
90 °C to RT, 7 h, 82% (2 steps)

NH2NH2,
Et3N
EtOH
50 °C, 6 h




Ni (Raney)
H2O, i-PrOH
50 °C, 60 min, 50%
"The yield was 100 % brsm."
