Synthesis of Erythromycin A
C38H69NO12
Principal investigator | Robert B. Woodward |
---|---|
Publication year | 1981 |
Synthesis type | Total |
Number of steps | 50 (4 parts) |
References |
Part 1 of 4
+
NaH
DMSO, THF
RT
AcOH
H2O
RT
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)."
MsCl
Pyr
RT
Al2O3
EtOAc
RT, 12% (5 steps)
"The product was cristallized to optical purity from the enantioenriched mixture."
NaBH4
MeOH
0 °C
- KH
- MeOCH2I
THF
0 °C
OsO4
Et2O
RT
TsOH,
Me2C(OMe)2
CH2Cl2
0 °C, 74% (4 steps)
Part 2 of 4
CF3CO2H
CH2Cl2
RT
Part 3 of 4
Ni (Raney)
EtOH
Reflux
- O3
- Me2S
CH2Cl2, MeOH
-78 °C to RT, 80% (3 steps)
Part 4 of 4
+
+
+
+
- KH
- AcCl
HMPA, THF
-78 to 0 °C
NaBH4
MeOH
-20 °C
MsCl,
DMAP
MeOH, Pyr
0 °C
LiAlH4
Et2O
-20 °C
Ac2O,
DMAP
CH2Cl2
0 °C, 92% (2 steps)
Ni (Raney)
DMF, EtOH
Reflux
- O3
- Me2S
CH2Cl2, MeOH
-78 °C to RT, 66% (3 steps)
- (CH2NMe2)2 , t-BuLi
- AcOH
THF
-110 °C, 90%
Na2CO3
MeOH
RT
DMAP,
(PhOCH2CO)2O
CH2Cl2, Pyr
0 °C
MsCl
Pyr
0 °C
LiOH,
H2O2
H2O, THF
RT, 75% (4 steps)
LiN3
H2O, HMPA
60 °C, 75%
PtO2,
H2
1 atm
THF
RT
NH2OH.HCl,
KH2PO4
H2O, MeOH
Reflux
Et3N
CH2Cl2
RT, 70% (4 steps)
Mesitaldehyde dimethyl acetal,
CF3CO2H
CH2Cl2
0 °C, 85%
EtSLi
HMPA
30 °C
Et3N
CH2Cl2
0 °C
p-PhBzCl,
DMAP
CH2Cl2, Et3N
RT
NaOH
H2O, i-PrOH, THF
RT, 70% (2 steps)
CF3CO2H,
SiO2
CH2Cl2, H2O
RT, 100%
AgOTf
CH2Cl2, PhMe
RT, 36%
Pb(ClO4)2
MeCN
RT
H2O
MeOH
20% (2 steps)
Na(Hg)
MeOH
75%
NCS
Pyr
RT
AgF
HMPA
70 °C
H2O
5 °C, 40% (3 steps)