Synthesis of Cylindrospermopsin

Structure of Cylindrospermopsin

C15H21N5O7S

Principal investigatorBarry B. Snider
Publication year2000
Synthesis typeTotal
Number of steps 24 (3 parts)
References
Part 1 of 3
intermediate structure
POCl3, PCl5
Reflux, 2 d
intermediate structure
MeOH
0 °C to RT, 12 h, 57% (2 steps)
intermediate structure
LiBH4
EtOH, THF
RT, 2 h, 93%
intermediate structure
Dess-Martin Periodinane
CH2Cl2
RT, 60 min, 90%
intermediate structure
Part 2 of 3
intermediate structure + intermediate structure
ClCO2CH2CCl3
THF
-30 °C, 2.5 h, 49%
"The yield was 87 % brsm."
intermediate structure
  1. TMSCl
  2. VinylMgBr
  3. CuBr.Me2S
THF
-78 °C, 2 h, 92%
intermediate structure
Zn
AcOH, CH2Cl2
RT, 5 h, 96%
intermediate structure
Li(s-Bu)3BH
THF
-78 °C, 2 h, 94%
intermediate structure
Na2CO3, ClCO2Bn
THF
RT, ON, 96%
intermediate structure
DMAP, Imidazole, TBSCl
CH2Cl2
RT, ON, 89%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
EtMgBr
THF
0 °C to RT, 4 h, 69%
"The yield was 83 % brsm."
intermediate structure
Imidazole, TBSCl
CH2Cl2
RT, 5 h, 88%
intermediate structure
  1. Me2S
  2. O3
CH2Cl2
-78 °C, 20 min, 72%
intermediate structure
BnNH2, Na2SO4, NaBH3CN
AcOH, MeOH, PhMe
RT, 4 h, 68%
intermediate structure
H2, Pd/C
MeOH
RT, ON
intermediate structure
BrCN
PhMe
RT, 5 h
intermediate structure
NaH, ClCO2Bn
THF
0 °C to RT, 8 h, 45% (3 steps)
intermediate structure
n-Bu4N+ F-
THF
RT, ON, 83%
intermediate structure
MnO2
CH2Cl2
RT, 60 min, 87%
intermediate structure
Ac2O
Pyr
RT, ON, 87%
intermediate structure + intermediate structure
CuBr2
EtOAc
35 °C, 20 min
intermediate structure
H2, Pd(OH)2/C
MeOH
RT, 8 h, 42% (2 steps)
"Also isolated was the C7-epimer (28 % yield)."
intermediate structure
HCl
H2O
100 °C, 6 h, 95%
intermediate structure
Na2SO4, SO3.DMF
Pyr
RT, ON, 50-70%
intermediate structure