Hydrochloric Acid → Podophyllotoxin

HRID 1285477Notes

Reaction equation

HRID 1285477 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:13]2[C@@H:22]3[C:23]([O:25][CH2:26][C@@H:21]3[C@@H:20]([OH:27])[C:19]3[CH:18]=[C:17]4[O:28][CH2:29][O:30][C:16]4=[CH:15][C:14]2=3)=[O:24])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].Cl.C(=O)([O-])[O-].[Ca+2]>C(O)(=O)C>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([C@H:13]2[C@H:22]3[C:23]([O:25][CH2:26][C@@H:21]3[C@@H:20]([OH:27])[C:19]3[CH:18]=[C:17]4[O:28][CH2:29][O:30][C:16]4=[CH:15][C:14]2=3)=[O:24])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10112Calcium CarbonateHCID 72435Picropodophyllin

Product 1

HCID 10607Podophyllotoxin

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

The first synthesis of podophyllotoxin, compound 6 (Scheme 2), was reported by Gensler and coworkers [J. Am. Chem. Soc., 76: 5894 (1954); J. Am. Chem. Soc., 76: 315 (1954)]. ##STR13## Stobbe condensation of 1-(3',4',5'-trimethoxybenzoyl)-3,4-methylenedioxybenzene 26 with ethyl succinate followed by saponification and hydrogenation gave the saturated dibasic acid 27. Conversion to the anhydride followed by intramolecular Friedel-Crafts acylation and then esterification gave the cyclic keto-ester 28. Condensation with ethyl formate followed by sodium borohydride reduction and saponification afforded the dihydroxy acid 29. Treatment with 10% aqueous sulfuric acid gave α-apopicropodophyllotoxin 30 which was converted to picropodophyllotoxin 15 by treatment with dry HCl in glacial acetic acid followed by aqueous calcium carbonate.

Sources & evidence

ORD record
ord-6fda770985a648ce8fbfdbd2302bb89f
Source dataset
uspto-grants-1986_01
Patent number
US04567253

Reaction notes

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