A Simplified Procedure for Indole Alkaloid Extraction from Catharanthus roseus Combined with a Semi-synthetic Production Process for Vinblastine

Abstract

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 semisynthesis of the anti-cancer bisindole alkaloid vinblastine. The coupling reaction involved oxidation of catharanthine in aqueous acidic medium by singlet oxygen ( 1 O 2 ), continuously produced in situ by the reaction between H 2 O 2 with NaClO. An excess of NaBH 4 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

Synthesis and study of a molecularly imprinted polymer for the specific extraction of indole alkaloids from Catharanthus roseus extracts

“…As catharanthine has a pK a significantly higher than vindoline, it is possible to extract separately these two alkaloids by varying amounts of hydrochloric acid and triethylamine in the mobile or station- ary phases. The basic character of these two monomeric indole alkaloids has also been utilized during the solid-liquid extraction of dried leaves of C. roseus under acidic conditions [12,13]. Moreover, Verma et al [14] have compared various quantitative extraction techniques such as supercritical fluid extraction, Soxhlet extraction, ultrasound-assisted solid-liquid extraction and hot water extraction.…”

Effects of PEG-induced drought stress on regulation of indole alkaloid biosynthesis in Catharanthus roseus

“…Catharanthus roseus (C. roseus) is a highly exploited perennial herbaceous flowering medicinal plant for its many valuable terpenoid indole alkaloids (TIAs) (Ganapathi & Kargi 1990) such as anti-cancer bisindole alkaloid vinblastine (VBL) and vincristine (VCR) (Sreevalli et al 2004;Verma et al 2007). Currently, chemical synthesis and metabolic engineering plant cell or tissue culture (Whitmer et al 1998;Hughes & Shanks 2002) are alternative methods for the synthesis and production of TIAs.…”

Endophytic bacteria of Catharanthus roseus as an alternative source of Vindoline and application of response surface methodology to enhance its production

“…Alkaloids have also been detected in endophytes isolated from Salvadora oleoides, Tabebuia argentea, Pinus roxburghii and Urospermum picroides by phytochemical analysis [36]. Verma et al [37] studied vinblastine and catharanthine yields as a function of pH and similar results were obtained, which is to be expected because vindoline, vinblastine and catharanthine have a similar nature as they belong to the group of terpenoid indole alkaloids. In earlier studies, HPLC analysis of the secondary metabolite profiles of C. roseus gave a similar result in which the retention time of vindoline was found to be 13.5 min.…”