Enzymic Coupling of Catharanthine and Vindoline to form 3′,4′-Anhydrovinblastine by Horseradish Peroxidase

Anne E. Goodbody; Tsuyoshi Endo; John Vukovic; James P. Kutney; Lewis S. L. Choi; Masanaru Misawa

doi:10.1055/s-2006-962371

Planta Medica, Table of Contents

Planta Med 1988; 54(2): 136-140
DOI: 10.1055/s-2006-962371

Papers

Enzymic Coupling of Catharanthine and Vindoline to form 3′,4′-Anhydrovinblastine by Horseradish Peroxidase

Anne E. Goodbody¹ , Tsuyoshi Endo² , John Vukovic¹ , James P. Kutney³ , Lewis S. L. Choi³ , Masanaru Misawa¹

¹Allelix Inc., 6850 Gorewary Drive, Mississauga, Ontario, L4V 1P1, Canada.
²Research Center for Cell and Tissue Culture, Faculty of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
³Department of Chemistry, University of British Columbia, Vancouver, British Columbia, V6T 1W5, Canada.

Abstract

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Abstract

The synthesis of 3′, 4′- anhydrovinblastine (AVLB) from catharanthine and vindoline was achieved through the enzymic action of horseradish peroxidase (HRP), followed by sodium borohydride reduction. It is proposed that the peroxidase enables the condensation of catharanthine and vindoline to an iminium intermediate, which is then reduced by the borohydride to AVLB. Catharanthine was apparently involved in other reactions, in addition to the coupling with vindoline, and the time at which its utilization was complete corresponded with the initiation of degradation of the putative iminium intermediate. There was an absolute requirement for either hydrogen peroxide or FMN and manganese chloride, but the latter combination is thought to generate hydrogen peroxide in situ by a light-activated mechanism. HRP types of varying purities and isozymic compositions all exhibited comparable coupling activities. AVLB yields of between 40 and 50% were reached under optimized conditions.

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