A simplified procedure for indole alkaloid extraction from Catharanthus roseus combined with a semi-synthetic production process for vinblastine.
Dried leaves of Catharanthus roseus were extracted with aqueous acidic 0.1 M solution of HCl. Alkaloid-embonate complexes were obtained as precipitates by treating the extract with an alkaline (NaOH) solution of embonic acid (4,4-methylene-bis-3-hydroxynaphtalenecarboxylic acid). The precipitate mainly consisted of catharanthine and vindoline embonates and it was directly used as the starting material for a semi-synthesis of the anti-cancer bisindole alkaloid vinblastine. The coupling reaction involved oxidation of catharanthine in aqueous acidic medium by singlet oxygen ((1)O2), continuously produced in situ by the reaction between H2O2 with NaClO. An excess of NaBH4 was used for the reduction step. Analysis of the reaction mixture indicated a maximum yield of 20% for vinblastine at pH 8.3, based on the initial amount of catharanthine concentration. Direct-injection electrospray ionization mass spectrometry in positive ion mode was used for the identification of vinblastine. The mass spectra of vinblastine were dominated by the corresponding protonated molecular ion [M+H]+ at m/z 811 and the characteristic fragment ions matched with those of the standard compound.
Verma
Arvind
A
Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, 00014 University of Helsinki, Finland. arvind.verma@helsinki.fi
Laakso
Into
I
Seppänen-Laakso
Tuulikki
T
Huhtikangas
Aarre
A
Riekkola
Marja-Liisa
ML
D030008:Catharanthus / Q000737:chemistry*; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification*; D021241:Spectrometry, Mass, Electrospray Ionization; D014747:Vinblastine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D014748:Vinca Alkaloids / Q000737:chemistry
D026121:Indole Alkaloids; D014748:Vinca Alkaloids; C009667:vindoline; D014747:Vinblastine; C017836:catharanthine