Synthesis of Erythromycin A

C38H69NO12
Principal investigator | Pierre Deslongchamps |
---|---|
Publication year | 1985 |
Synthesis type | Formal |
Number of steps | 43 (linear) |
References |
Part 1 of 1
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- n-BuLi
- TMSCl
THF
-78 to 0 °C, 4 h, 80%

Lindlar Catalyst,
H2
Cyclohexane
15 °C, 30 h, 100%

TMSOTf
CH2Cl2
-78 °C, 5 h, 84%

Pyr.TsOH
CH2Cl2
Reflux, 40 h, 84%

SeO2,
Pyr
Xylene(s)
140 °C, 5 h

HCrO3Cl.Pyr
3 Å MS
CH2Cl2
RT, 60% (2 steps)



K2CO3
MeOH
RT, 60 min, 94%


- i-PrN(Cy)Li
- PhSeBr
DME
-78 °C, 90 min, 89%

H2O2,
Pyr
CH2Cl2, H2O
RT to 45 °C, 86%

Pd/C
Xylene(s)
138 °C, 2 h, 100%

LiAlH4
THF
0 °C to RT, 2 h, 90%

DMAP,
(EtCO)2O
Pyr
RT, 60 min, 99%

i-Pr2NEt,
MeOCH2Cl
CH2Cl2
50 °C, 4 h, 90%


KHCO3,
KI3
H2O, MeOH
0 °C to RT, 15.5 h, 65% (2 steps)

Ni (Raney),
NaHCO3,
H2
3.5 atm
EtOH, H2O
RT, 24 h, 60%
"Also isolated was the C6-epimer (25 % yield)."

LiAlH4
THF
0 °C to RT, 65 min, 90%

TBDPSCl,
Imidazole
DMF
RT, 60 min, 95%

BzCl
Pyr
70 °C, 24 h, 78%


n-Bu4N+ F-
THF
70 °C, 2 h, 95%

HCrO3Cl.Pyr,
NaOAc
3 Å MS
CH2Cl2
RT, 30 min, 85%


HCl
H2O, MeOH
RT, 8 h, 93%

K2CO3
MeOH
RT, 2 h, 95%

ClCO2Ph,
Pyr
CH2Cl2
0 °C, 30 min, 92%

Imidazole
Xylene(s)
100 °C, 40 min, 98%

TsOH
AcOH, CF3CO2H
70 °C, 30 min, 81%

HCl
Acetone, H2O
RT, 24 h, 68%

DMAP,
Ac2O
CH2Cl2
RT, 20 h, 74%

NaBH4
MeOH, THF
RT, 90 min, 48%
"Also isolated was the C9-epimer (24% yield)."

MsCl
Pyr
0 °C, 20 h, 100%

LiN3
HMPA
60 °C, 60 min, 91%

PtO2,
H2
THF
RT, 3 h, 100%

PhH
Reflux, 5 d, 76%

LiI
Pyr
Reflux, 5 d

NaOH
H2O, MeOH
RT, 70 h

CH2N2
Et2O
RT, 10 min, 60% (3 steps)

Pd/C,
H2
EtOAc
RT, 11.5 h, 85%

Remaining...
1.1% (14 Steps)
"See: J. Am. Chem. Soc. 1981, 103, 3215."
