Synthesis of Chlorophyll A
C55H72MgN4O5
| Principal investigator | Robert B. Woodward |
|---|---|
| Publication year | 1960 |
| Synthesis type | Formal |
| Number of steps | 49 (7 parts) |
| References |
Part 1 of 7
Part 2 of 7
H2SO4
40 °C, 20 min, 90%
HO(CH2)2NH2
170 °C, 60 min, 84-87%
Br2
H2O, MeOH
Reflux, 4 min, 68-70%
NaOH
H2O
100 °C, 3.5 h, 83%
NaHCO3,
NaBH4
H2O
RT, 40 min, 87%
NaOAc.3H2O,
KOAc
100-135 °C, 25 min, 50-58%
H2,
PtO2
3 atm
MeOH
RT, 3 h, 85-93%
Part 3 of 7
AcCl,
AlCl3
CH2Cl2
Reflux, 2 h, 86%
See the Friedel-Crafts Acylation
"The starting material is an intermediate of the second part of this synthesis."
SO2Cl2
AcOH
55 °C, 90 min, 84%
Part 4 of 7
- Br2 , SO2Cl2
- H2O
AcOH
0 to 60 °C, 6.5 h, 70-75%
Cu-Bronze
230-240 °C, 60 min, 72%
KOH
EtOH, H2O
Reflux, 2.5 h, 90%
Cu-Bronze
220-240 °C, 60 min, 80%
Part 5 of 7
Malonic Acid,
PhNH2
EtOH
Reflux, 8 h, 70-75%
See the Knoevenagel Condensation
"The starting material is an intermediate of the second part of this synthesis."
Ni (Raney),
NaOH,
H2
2 atm
H2O
RT, 12 h, 90-92%
- SO2Cl2
- H2O
Et2O
-15 °C to RT, ON, 85-90%
NaOH
H2O
180 °C, 90 min
CH2N2
Et2O, MeOH
RT, 75-80% (2 steps)
Part 6 of 7
+
+
+
+
NaOH
H2O
95 °C, 15 min
CH2N2
H2O, MeOH
RT, 90 min, 84% (2 steps)
EtNH2,
HBr
AcOH, H2O
0 °C, 45 min, 94%
H2S,
NaOMe
MeOH, PhH
RT, 5 min, 86%
Part 7 of 7
+
+
+
HBr
Et2O, H2O, MeOH
-25 to 0 °C, 56%
NaBH4
H2O
RT
+
- HCl
- I2
CH2Cl2, MeOH, PhH
RT, 60 min
Ac2O
Pyr
50-55 °C, 60 min, 48% (3 steps)
O2
AcOH
95 °C, 60 min, 91%
AcOH
Reflux, 31.5 h, 59%
HCl
H2O, MeOH
Reflux, 18 h, 75%
O2
hν
CH2Cl2
0 °C, 35 min, 59%
KOH
CH2Cl2, MeOH
RT, 60 min, 22%
NaOH
Dioxane , H2O
RT, 12 h
"The enantiomers were resolved with (-)-Quinine (4 % yield)."
CH2N2
Et2O, MeOH
RT, 20 min, 60% (2 steps)
"Relay point."
HCN,
Et3N
CH2Cl2
0 °C to RT, 5 min, 78%
Zn
AcOH, CH2Cl2
RT, 1 min
CH2N2
Et2O, MeOH
RT, 10 min, 9% (2 steps)
HCl
MeOH
0 °C to RT, 16 h, 36%
Remaining...
23% (4 steps)
"See: Fortschr. Chem. Forsch. 1952, 2, 538 and
Tetrahedron 1981, 37, 399."