Synthesis of Pactamycin

Structure of Pactamycin

C28H38N4O8

Principal investigatorStephen Hanessian
Publication year2011
Synthesis typeTotal
Number of steps 35 (linear)
References
Part 1 of 1
intermediate structure
TsOH, BnOH
PhH
Reflux, 24 h, 67%
intermediate structure
Et3N, p-MeOBzCl
CH2Cl2
RT, 2 h, 64%
intermediate structure
SOCl2
MeCN
0 °C to RT, 10 h, 85%
intermediate structure + intermediate structure
TMS2NLi
THF
-78 °C, 55 min
See the Aldol Addition
intermediate structure
2,6-Lutidine, TESOTf
CH2Cl2
0 °C to RT, 2 h, 67% (2 steps)
intermediate structure
i-Bu2AlH
CH2Cl2
-78 °C
intermediate structure
MeMgBr
Et2O
0 °C, 60 min, 87% (2 steps)
intermediate structure
(COCl)2, DMSO, Et3N
CH2Cl2
-78 to 0 °C, 105 min, 91%
See the Swern Oxidation
intermediate structure
  1. Me2S
  2. O3
CH2Cl2
-78 °C to RT, ON, 84%
intermediate structure
i-Pr2NEt, TiCl4, TMSCl
CH2Cl2
0 °C, 20 min, 85%
See the Aldol Addition
intermediate structure
Pyr, Cl3CCOCl
CH2Cl2
RT, 8 h, 89%
intermediate structure
H2O2, NaOH
CH2Cl2, H2O, MeOH
0 °C, 2 h, 75%
"Also isolated was the TES-deprotected product (16 % yield)."
intermediate structure
NaBH4, CeCl3.7H2O
CH2Cl2, MeOH
0 °C, 70 min, 92%
See the Luche Reduction
intermediate structure
Pyr, Tf2O
CH2Cl2
-78 to 0 °C, 60 min
intermediate structure
n-Bu4N+ N3-
PhMe
RT, 3 d, 86% (2 steps)
intermediate structure
CF3CO2H
H2O, MeCN
0 °C, 4 h, 93%
intermediate structure
Dess-Martin Periodinane
CH2Cl2
0 °C to RT, 2 h, 96%
intermediate structure
MeMgBr
THF
-78 °C, 3 h, 91%
intermediate structure
n-Bu4N+ F-
THF
0 °C to RT, 90 min, 95%
intermediate structure
Zn(OTf)2
AcOH
80 °C, 2 d
intermediate structure
K2CO3
MeOH
0 °C to RT, 60 min, 87% (2 steps)
intermediate structure
DMAP, Et3N, TBDPSCl
CH2Cl2
0 °C to RT, 4 h, 96%
intermediate structure
Pyr, Tf2O
CH2Cl2
-78 to 0 °C, 60 min, 96%
intermediate structure + intermediate structure
Yb(OTf)3
PhMe
80 °C, 9 h, 81%
"The yield was 91 % brsm."
intermediate structure
HCl
H2O, THF
0 °C to RT, 14 h, 63%
"The yield was 83 % after two cycles."
intermediate structure
TASF
CH2Cl2
0 °C to RT, 60 min, 95%
intermediate structure
Camphorsulfonic acid, 2,2-Dimethoxypropane
CH2Cl2
0 °C to RT, 2 h, 86%
intermediate structure
Et3N, ClCO2CCl3
THF
-46 °C, 15 min, 89%
intermediate structure
Me2NH
-46 °C to RT, , 97%
intermediate structure
i-Bu2AlH
CH2Cl2
-78 °C, 90 min, 90%
intermediate structure
NMO, OsO4
Acetone, H2O, THF
0 °C to RT, 2 h
intermediate structure
NaIO4
H2O, THF
RT, 3 h, 80% (2 steps)
intermediate structure
CF3CO2H
H2O, MeCN
0 °C to RT, 45 min, 85%
intermediate structure + intermediate structure
K2CO3
DMA
RT, 70 min, 96%
intermediate structure
H2, Lindlar Catalyst
EtOH, MeOH
RT, 3 h, 85%
intermediate structure