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
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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
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- 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)
