Synthesis of Cortistatin A

Structure of Cortistatin A

C30H36N2O3

Principal investigatorMatthew D. Shair
Publication year2008
Synthesis typeTotal
Number of steps 25 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
NaH
DMSO
RT, 21 h, 63%
"The starting material was obtained in two steps from the Hajos-Parrish ketone."
intermediate structure
2,6-Lutidine, TBSOTf
CH2Cl2
0 °C, 2 h
intermediate structure
H2, Pd/C
EtOAc
RT, 20 h
intermediate structure
HF, mCPBA, NaHCO3
PhMe, THF
-10 to 0 °C, , 66% (3 steps)
intermediate structure
i-Pr2NEt, MeO(CH2)2OCH2Cl
DCE
80 °C, 13 h, 88%
intermediate structure
Pyr.TsOH
Acetone, H2O
60 °C, 5 h
intermediate structure
NaOMe
MeOH
70 °C, 2 h, 49% (2 steps)
See the Aldol Addition
intermediate structure
Pyr, SOCl2
CH2Cl2
10 °C, 30 min
intermediate structure
PhNTf2, TMS2NNa
THF
-78 to 0°C, 3 h
intermediate structure + intermediate structure
Pd(PPh3)4
THF
RT, 30 min, 62% (3 steps)
intermediate structure
KOt-Bu, CHBr3
Hexane(s)
0 °C, 2 h
intermediate structure
TASF
DMF
80 °C, 30 min, 66% (2 steps)
intermediate structure + intermediate structure
K2CO3, Pd(PPh3)4
H2O, THF
80 °C, 5 h, 84%
See the Suzuki Coupling
intermediate structure
K2CO3, MsNH2, K3Fe(CN)6, K2OsO2(OH)4, (DHQD)2PHAL
H2O, t-BuOH
intermediate structure
Ac2O, Et3N
CH2Cl2
RT, 18 h, 51% (2 steps)
intermediate structure
Pyr.HF
THF
RT, 5 min
intermediate structure
Dess-Martin Periodinane
CH2Cl2
RT, 60 min
intermediate structure
ZnBr2, Me2NH
MeCN
50 °C, 40 min, 65% (3 steps)
See the Prins Reaction
intermediate structure
n-Bu4N+ F-
THF
70 °C, 4 h, 70%
intermediate structure
NMO, n-Pr4N+ RuO4-
CH2Cl2
RT, 2.5 h, 100%
intermediate structure
K2CO3
MeOH
RT, 30 min, 82%
intermediate structure
Et3N, NH2NH2
EtOAc
80 °C, 6 h
intermediate structure
I2
THF
RT, 5 min
intermediate structure + intermediate structure
CuCl, LiCl, Pd(PPh3)4
DMSO
60 °C, 60 min, 61% (3 steps)
See the Stille Coupling
intermediate structure
Et3N
THF
60 °C, 9 h, 20%
intermediate structure