Synthesis of Cortistatin A

Structure of Cortistatin A

C30H36N2O3

Principal investigatorPhil S. Baran
Publication year2008
Synthesis typePartial
Number of steps 19 (linear)
References
J. Am. Chem. Soc. 2008, 130, 7241.
Part 1 of 1
intermediate structure
  1. BH3.THF
  2. 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]""
intermediate structure
TsOH, (CH2OH)2
PhMe
Reflux, 60 min, 92% (2 steps)
intermediate structure
t-BuOOH, DBU
THF
RT, 72 h, 82%
See the Michael Addition
intermediate structure
  1. NH4OAc , NaBH3CN
  2. Et3N , HCO2Et
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. PhSiH3 , O2 , Co(acac)2
  2. TsOH
  3. K2CO3 , MeOH
THF, HC(OMe)3
RT, 14 h, 63%
See the Mukaiyama Hydration
"Three stage, one pot reaction."
intermediate structure
PhI(OAc)2, Br2
hν
CH2Cl2
-30 °C, 10 h
intermediate structure
TMSCl, Imidazole
CH2Cl2
0 °C, 15 min, 57% (2 steps)
intermediate structure
LiCl, DBU
THF
RT, 24 h, 85%
intermediate structure
Special reagent
SmI2
THF, DMPU
-72 °C to RT, 35 min
intermediate structure
LiBr, Li2CO3
DMF
60 °C, 60 min, 63% (2 steps)
intermediate structure
  1. AlH3
  2. MeOH , K2CO3
THF
RT, 13 h
intermediate structure
Ac2O, DMAP, Et3N
CH2Cl2
RT, 5 h, 89% (2 steps)
intermediate structure
2,6-Di-tert-butylpyridine, MgBr2.OEt2
PhH
78 °C, 90 min
intermediate structure
  1. Pyr.TsOH
  2. K2CO3
H2O, MEK
90 °C to RT, 7 h, 82% (2 steps)
intermediate structure
NH2NH2, Et3N
EtOH
50 °C, 6 h
intermediate structure
I2, Et3N
THF
RT, 5 min
See the Barton Vinyl Iodide Synthesis
intermediate structure + intermediate structure
Pd(PPh3)4, LiCl, CuCl
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
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