Synthesis of Erythromycin A

Structure of Erythromycin A

C38H69NO12

Principal investigatorPierre Deslongchamps
Publication year1985
Synthesis typeFormal
Number of steps 43 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
  1. n-BuLi
  2. TMSCl
THF
-78 to 0 °C, 4 h, 80%
intermediate structure
H2, Lindlar Catalyst
Cyclohexane
15 °C, 30 h, 100%
intermediate structure
TMSOTf
CH2Cl2
-78 °C, 5 h, 84%
intermediate structure
Pyr.TsOH
CH2Cl2
Reflux, 40 h, 84%
intermediate structure
SeO2, Pyr
Xylene(s)
140 °C, 5 h
intermediate structure
HCrO3Cl.Pyr
CH2Cl2
RT, , 60% (2 steps)
intermediate structure
  1. MeLi
  2. CuBr
  3. Bz2O2
Et2O
-78 to 0 °C, 45 min, 75%
intermediate structure
MeMgBr
Et2O
-78 °C, 60 min, 63%
intermediate structure
K2CO3
MeOH
RT, 60 min, 94%
intermediate structure
LiCl
DMSO, H2O
170 °C, 70 min, 83%
intermediate structure
  1. i-PrN(Cy)Li
  2. PhSeBr
DME
-78 °C, 90 min, 89%
intermediate structure
H2O2, Pyr
CH2Cl2, H2O
RT to 45 °C, , 86%
intermediate structure
Pd/C
Xylene(s)
138 °C, 2 h, 100%
intermediate structure
LiAlH4
THF
0 °C to RT, 2 h, 90%
intermediate structure
(EtCO)2O, DMAP
Pyr
RT, 60 min, 99%
intermediate structure
MeOCH2Cl, i-Pr2NEt
CH2Cl2
50 °C, 4 h, 90%
intermediate structure
  1. i-Pr2NLi
  2. TBSCl
THF, HMPA
-78 °C, 2.5 h
intermediate structure
KI3, KHCO3
MeOH, H2O
0 °C to RT, 15.5 h, 65% (2 steps)
intermediate structure
H2, Ni (Raney), NaHCO3
EtOH, H2O
RT, 24 h, 60%
"Also isolated was the C6-epimer (25 % yield)."
intermediate structure
LiAlH4
THF
0 °C to RT, 65 min, 90%
intermediate structure
TBDPSCl, Imidazole
DMF
RT, 60 min, 95%
intermediate structure
BzCl
Pyr
70 °C, 24 h, 78%
intermediate structure
  1. TMS2NK
  2. BnBr
THF
0 °C to RT, 20 min, 92%
intermediate structure
n-Bu4N+ F-
THF
70 °C, 2 h, 95%
intermediate structure
HCrO3Cl.Pyr, NaOAc
CH2Cl2
RT, 30 min, 85%
intermediate structure
EtCO2Me, Cp2ZrCl2, i-Pr2NLi
THF
-78 °C to RT, 2 h, 60%
See the Aldol Addition
intermediate structure
HCl
MeOH, H2O
RT, 8 h, 93%
intermediate structure
K2CO3
MeOH
RT, 2 h, 95%
intermediate structure
ClCO2Ph, Pyr
CH2Cl2
0 °C, 30 min, 92%
intermediate structure
Imidazole
Xylene(s)
100 °C, 40 min, 98%
intermediate structure
TsOH
AcOH, CF3CO2H
70 °C, 30 min, 81%
intermediate structure
HCl
Acetone, H2O
RT, 24 h, 68%
intermediate structure
Ac2O, DMAP
CH2Cl2
RT, 20 h, 74%
intermediate structure
NaBH4
THF, MeOH
RT, 90 min, 48%
"Also isolated was the C9-epimer (24% yield)."
intermediate structure
MsCl
Pyr
0 °C, 20 h, 100%
intermediate structure
LiN3
HMPA
60 °C, 60 min, 91%
intermediate structure
H2, PtO2
THF
RT, 3 h, 100%
intermediate structure
PhH
Reflux, 5 d, 76%
intermediate structure
LiI
Pyr
Reflux, 5 d
intermediate structure
NaOH
MeOH, H2O
RT, 70 h
intermediate structure
CH2N2
Et2O
RT, 10 min, 60% (3 steps)
intermediate structure
H2, Pd/C
EtOAc
RT, 11.5 h, 85%
intermediate structure
Remaining...
1.1% (14 Steps)
"See: J. Am. Chem. Soc. 1981, 103, 3215."
intermediate structure