Synthesis of Dragmacidin F

Structure of Dragmacidin F

C25H20BrN7O3

Principal investigatorBrian M. Stoltz
Publication year2004
Synthesis typeTotal
Number of steps 25 (3 parts)
References
Part 1 of 3
intermediate structure
Amberlyst 15
DMF, PhH
Reflux, 16 h, 99%
intermediate structure
DMAP, Et3N, TBSCl
DMF
-20 to -5 °C, 2.5 h, 69%
intermediate structure
H2Cr2O7.2Pyr, Celite
MeCN
45 °C, 24 h, 91%
intermediate structure
KOt-Bu, Ph3P+CH3 Br-
THF
65 °C, 2 h, 76%
See the Wittig Reaction
intermediate structure
H2, Pd/C
MeOH
0 °C, 7 h, 99%
intermediate structure
NHMeOMe.HCl, CDI
CH2Cl2
RT, 3.5 h, 93%
intermediate structure + intermediate structure
THF
-78 to 0 °C, 30 min, 71%
intermediate structure
Pd(OAc)2
AcOH, DMSO, t-BuOH
60 °C, 10 h, 74%
intermediate structure
H2, Pd/C
EtOAc
RT, 30 min, 99%
intermediate structure
MeI, NaH
THF
0 °C to RT, 60 min, 96%
intermediate structure
NBS
THF
0 °C to RT, 15 min, 96%
intermediate structure
  1. n-BuLi
  2. i-PrOBpin
THF
-78 °C, 15 min, 73%
intermediate structure
Part 2 of 3
intermediate structure
KOH, TsCl, n-Bu4N+ HSO4-
H2O, PhMe
RT, 4 h, 98%
intermediate structure
Hg(OAc)2, HClO4
AcOH, H2O
RT, 24 h, 99%
intermediate structure
  1. BH3.THF
  2. H2O
THF
RT, 60 min, 85%
intermediate structure + intermediate structure
Na2CO3, Pd(PPh3)4
H2O, MeOH, PhH
RT, 72 h, 71%
See the Suzuki Coupling
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
Na2CO3, Pd(PPh3)4
H2O, MeOH, PhH
50 °C, 2.5 d, 77%
See the Suzuki Coupling
intermediate structure
LiBF4
H2O, MeCN
45-50 °C, 31 h, 98%
intermediate structure
Dess-Martin Periodinane
CH2Cl2
RT, 3 min, 90%
intermediate structure
NaOAc, NH2OH.HCl
H2O, MeOH
RT, 8 h, 98%
intermediate structure
KOH, TsCl, n-Bu4N+ Br-
H2O, PhMe
0 °C, 2 h, 98%
intermediate structure
HCl, KOH
EtOH, H2O
0 to 60 °C, 13 h
intermediate structure
K2CO3
H2O, THF
RT, 10 min, 96% (2 steps)
intermediate structure
TMSI
MeCN
60 °C, 48 h, 95%
intermediate structure
NaOH, NH2CN
H2O
60 °C, 2 h, 86%
intermediate structure