Synthesis of Camptothecin

Structure of Camptothecin

C20H16N2O4

Principal investigator	Henry Rapoport
Publication year	1972
Synthesis type	Total
Number of steps	15 (linear)
References	J. Am. Chem. Soc. 1972, 94, 8615. J. Am. Chem. Soc. 1972, 94, 8613. J. Am. Chem. Soc. 1975, 97, 159.

Part 1 of 1

intermediate structure

H2, NH3, Rh/Al2O3

2 atm

H2O

RT, 24 h

intermediate structure

H2SO4

3 A MS

EtOH, PhH

Reflux, 24 h, 84% (2 steps)

See the Fischer-Speier Esterification

intermediate structure

Special reagent

NaOAc

70-75 °C, 7 h, 80%

intermediate structure

KOt-Bu
H2O , HCl

PhMe, t-BuOH

0 °C to Reflux, ON, 100%

See the Dieckmann Condensation

intermediate structure

NaBH4, NaOH

H2O, MeOH

0 °C, 20.5 h, 87%

intermediate structure

Ac2O

2.5 h, 84%

intermediate structure

SeO2

AcOH

100 °C, 15 min

intermediate structure

H2SO4, Ac2O

AcOH

140 °C, 30 min, 69% (2 steps)

intermediate structure

K2CO3

MeOH

RT, 30 min, 100%

intermediate structure

EtCO2H, n-PrC(OMe)3

145 °C, 3 h, 75%

See the Johnson-Claisen Rearrangement

intermediate structure

DCC, H3PO4

DMSO

RT, 30 h, 76%

See the Pfitzner-Moffatt oxidation

intermediate structure

Special reagent

TsOH

Dean-Stark

PhMe

Reflux, 3 h, 79%

See the Friedländer synthesis

intermediate structure

SeO2

AcOH

80 °C, 2.5 h

intermediate structure

H2O, H2SO4

DME

50 °C, 7 h, 79% (2 steps)

See the Fischer-Speier Esterification

intermediate structure

O2, CuCl2, Me2NH

1 atm

DMF, H2O

RT, 5 h, 99%

intermediate structure

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