Synthesis of Aspidophytine

Structure of Aspidophytine

C22H26N2O4

Principal investigatorElias J. Corey
Publication year1999
Synthesis typeTotal
Number of steps 20 (3 parts)
References
Part 1 of 3
intermediate structure
SiO2, Fe
AcOH, PhMe
Reflux, 20 min, 71%
intermediate structure
KOH, MeI, n-Bu4N+ I-
THF
RT, 3 h, 94%
intermediate structure
POCl3
DMF
0 to 35 °C, 60 min, 99%
intermediate structure
NH4OAc
MeNO2
Reflux, 60 min, 92%
See the Henry Reaction
intermediate structure
LiAlH4
THF
0 °C to Reflux, 60 min, 88%
intermediate structure
Part 2 of 3
intermediate structure + intermediate structure
CeCl3
THF
0 °C, , 82%
intermediate structure
CBS Reagent, Catecholborane
CH2Cl2
-78 °C, 10 h, 94%
intermediate structure
Na(Hg)
MeOH
RT, 2 h, 82%
intermediate structure
Ac2O, DMAP
CH2Cl2, Et3N
RT, 60 min, 97%
intermediate structure
  1. i-Pr2NLi
  2. TBSCl
THF
-78 °C to Reflux, 4.5 h
intermediate structure
DMAP, EDC
i-PrOH
40 °C, 3 h, 57% (2 steps)
intermediate structure
NMO, OsO4
Acetone, H2O
RT, 6 h, 57%
intermediate structure
NaIO4
H2O, THF
RT, 35 min, 98%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
NaBH3CN, (CF3CO)2O
MeCN
0 °C to RT, 2.5 h, 66%
intermediate structure
NaOH
EtOH
75 °C, 20 h, 88%
intermediate structure
NaHCO3, K3Fe(CN)6
H2O, t-BuOH
RT, 5 min, 92%
intermediate structure
DMAP, OsO4
H2O, t-BuOH
intermediate structure
Pb(OAc)4
AcOH, CH2Cl2
-20 °C, 10 min, 71% (2 steps)
intermediate structure
  1. TMS2NK
  2. PhNTf2
THF
-78 °C, 30 min, 54%
intermediate structure
n-Bu3SnH, Pd(PPh3)4
THF
RT, 60 min, 86%
See the Stille Coupling
intermediate structure