Synthesis of Erythromycin A

Structure of Erythromycin A

C38H69NO12

Principal investigatorRobert B. Woodward
Publication year1981
Synthesis typeTotal
Number of steps 50 (4 parts)
References
Part 1 of 4
intermediate structure + intermediate structure
NaH
THF, DMSO
RT
intermediate structure
AcOH
H2O
RT
intermediate structure
D-Proline
MeCN
RT
See the Aldol Addition
"Also isolated was the C6-epimer (50:50 dr). Both diastereoisomers were obtained as an enantioenriched mixture (36 % ee)."
intermediate structure
MsCl
Pyr
RT
intermediate structure
Al2O3
EtOAc
RT, , 12% (5 steps)
"The product was cristallized to optical purity from the enantioenriched mixture."
intermediate structure
NaBH4
MeOH
0 °C
intermediate structure
  1. KH
  2. MeOCH2I
THF
0 °C
intermediate structure
OsO4
Et2O
RT
intermediate structure
Me2C(OMe)2, TsOH
CH2Cl2
0 °C, , 74% (4 steps)
intermediate structure
Part 2 of 4
intermediate structure
CF3CO2H
CH2Cl2
RT
intermediate structure
(CF3CO)2O, DMSO, i-Pr2NEt
CH2Cl2
-60 to 0 °C, , 85% (2 steps)
See the Swern Oxidation
intermediate structure
Part 3 of 4
intermediate structure
Ni (Raney)
EtOH
Reflux
intermediate structure
  1. o-NO2PhSeCN
  2. n-Bu3P
  3. H2O2
  4. H2O
THF
RT
intermediate structure
  1. O3
  2. Me2S
CH2Cl2, MeOH
-78 °C to RT, , 80% (3 steps)
intermediate structure
Part 4 of 4
intermediate structure + intermediate structure
MesLi
THF
-50 °C
See the Aldol Addition
intermediate structure
(CF3CO)2O, DMSO, i-Pr2NEt
CH2Cl2
-60 to 0 °C, , 76% (2 steps)
See the Swern Oxidation
intermediate structure
  1. KH
  2. AcCl
THF, HMPA
-78 to 0 °C
intermediate structure
NaBH4
MeOH
-20 °C
intermediate structure
MsCl, DMAP
MeOH, Pyr
0 °C
intermediate structure
BnSH, n-BuLi
THF
-50 °C, , 85% (4 steps)
intermediate structure
LiAlH4
Et2O
-20 °C
intermediate structure
Ac2O, DMAP
CH2Cl2
0 °C, , 92% (2 steps)
intermediate structure
Ni (Raney)
EtOH, DMF
Reflux
intermediate structure
  1. o-NO2PhSeCN
  2. n-Bu3P
  3. H2O2
  4. H2O
THF
RT
intermediate structure
  1. O3
  2. Me2S
CH2Cl2, MeOH
-78 °C to RT, , 66% (3 steps)
intermediate structure
EtCOSt-Bu, i-Pr2NLi
THF
-110 °C, , 85%
See the Aldol Addition
intermediate structure
  1. t-BuLi
  2. (CH2NMe2)2
  3. AcOH
THF
-110 °C, , 90%
intermediate structure
Na2CO3
MeOH
RT
intermediate structure
(PhOCH2CO)2O, DMAP
CH2Cl2, Pyr
0 °C
intermediate structure
MsCl
Pyr
0 °C
intermediate structure
LiOH, H2O2
THF, H2O
RT, , 75% (4 steps)
intermediate structure
LiN3
HMPA, H2O
60 °C, , 75%
intermediate structure
H2, PtO2
THF
RT
intermediate structure
ClCO2(p-NO2Ph), NaHCO3
CH2Cl2, H2O
RT
intermediate structure
NH2OH.HCl, KH2PO4
MeOH, H2O
Reflux
intermediate structure
Et3N
CH2Cl2
RT, , 70% (4 steps)
intermediate structure
Mesitaldehyde dimethyl acetal, CF3CO2H
CH2Cl2
0 °C, , 85%
intermediate structure
EtSLi
HMPA
30 °C
intermediate structure + intermediate structure
Et3N
CH2Cl2
0 °C
intermediate structure
PhMe
110 °C, , 70% (3 steps)
intermediate structure
p-PhBzCl, DMAP
CH2Cl2, Et3N
RT
intermediate structure
NaOH
THF, i-PrOH, H2O
RT, , 70% (2 steps)
intermediate structure
SiO2, CF3CO2H
CH2Cl2, H2O
RT, , 100%
intermediate structure + intermediate structure
AgOTf
CH2Cl2, PhMe
RT, , 36%
intermediate structure + intermediate structure
Pb(ClO4)2
MeCN
RT
intermediate structure
H2O
MeOH
20% (2 steps)
intermediate structure
Na(Hg)
MeOH
75%
intermediate structure
NCS
Pyr
RT
intermediate structure
AgF
HMPA
70 °C
intermediate structure
H2O
5 °C, , 40% (3 steps)
intermediate structure