Synthesis of Cortistatin A

Structure of Cortistatin A

C30H36N2O3

Principal investigatorPhil S. Baran
Publication year2008
Synthesis typePartial
Number of steps 19 (linear)
References
Part 1 of 1
intermediate structure
  1. BH3.THF
  2. H2O
  3. NaIO4
  4. 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]""
intermediate structure
(CH2OH)2, TsOH
PhMe
Reflux, 60 min, 92% (2 steps)
intermediate structure
DBU, t-BuOOH
THF
RT, 72 h, 82%
intermediate structure
  1. Et3N
  2. NaBH3CN
  3. HCO2Et
  4. NH4OAc
MeOH, THF
RT to 54 °C, 48 h, 73%
intermediate structure
n-Bu4N+ OAc-, Co(acac)2
PhH
90 °C, 24 h, 48%
"The yield was 76 % brsm."
intermediate structure
  1. K2CO3
  2. O2
  3. TsOH
  4. Co(acac)2
  5. PhSiH3
  6. MeOH
THF, HC(OMe)3
RT, 14 h, 63%
"Three stage, one pot reaction."
intermediate structure
Br2, PhI(OAc)2
CH2Cl2
-30 °C, 10 h
intermediate structure
Imidazole, TMSCl
CH2Cl2
0 °C, 15 min, 57% (2 steps)
intermediate structure
DBU, LiCl
THF
RT, 24 h, 85%
intermediate structure
SmI2
THF, DMPU
-72 °C to RT, 35 min
intermediate structure
LiBr, Li2CO3
DMF
60 °C, 60 min, 63% (2 steps)
intermediate structure
  1. K2CO3
  2. AlH3
  3. MeOH
THF
RT, 13 h
intermediate structure
Ac2O, DMAP, Et3N
CH2Cl2
RT, 5 h, 89% (2 steps)
intermediate structure
MgBr2.OEt2, 2,6-Di-tert-butylpyridine
PhH
78 °C, 90 min
intermediate structure
  1. K2CO3
  2. Pyr.TsOH
H2O, MEK
90 °C to RT, 7 h, 82% (2 steps)
intermediate structure
Et3N, NH2NH2
EtOH
50 °C, 6 h
intermediate structure
Et3N, I2
THF
RT, 5 min
intermediate structure + intermediate structure
CuCl, LiCl, Pd(PPh3)4
DMSO
RT, 10 min, 53% (3 steps)
See the Stille Coupling
intermediate structure
Ni (Raney)
H2O, i-PrOH
50 °C, 60 min, 50%
"The yield was 100 % brsm."
intermediate structure