Biosynthesis of the Indole Alkaloids. Cell‐free Systems from Catharanthus roseus Plants

Abstract

SummaryCell-free systems from Catharunthus roseus plants are utilized for various studies relating to the biosynthesis of indole alkaloids. Tryptamine (5) and secologanin (6), two fundamental building units, are shown to be incorporated into the alkaloid vindoline (7). In another study, catharanthine (18) and vindoline (7) are utilized by this enzyme system and coupled to the important bisindole biointermediate 3', 4'-anhydr~vinblastine~) (17). The latter substance is, in turn, incorporated and converted to the natural alkaloids leurosine (8), Catharine (9) and vinblastine (lo), thereby providing information about the biosynthesis of these complex molecules. High pressure liquid chromatography assay of the enzymic mixture sheds light on the enzymes involved in the coupling of 18 and 7.The utilization of cell-free systems from Catharanthus roseus seedlings, plants or tissue cultures in indole alkaloid biosynthesis has been the subject of a number of recent publications from several laboratories. Scott & Lee [S] were the first to describe a cell-free system capable of synthesizing ajmalicine (1) and geissoschizine (4) from tryptamine (5) and secologanin (6; s. below). Subsequent studies in their or other laboratories [6-181 have provided information on some of the stages relating to the biosynthesis of such CorynanthP type alkaloids. For example, the condensation of tryptamine and secologanin for the biosynthesis of 1, 4 and the related alkaloids 19-epiajmalicine (2) and tetrahydroalstonine (3) occurs in the presence of NADPH as a co-factor. More recent studies, particularly by Scott, Zenk, Stockigt and their co-workers, have provided detailed information on the later-stage biointermediates [ 181. While these investigations were underway we addressed ourselves to the biosyntheses of Aspidosperma and fboga alkaloids. We wish to describe our experiments concerning the use of cell-free systems to demonstrate certain aspects of the biosynthesis of the alkaloid vindoline (7; s.

Cell and tissue cultures ofCatharanthus roseus (L.) G. Don: a literature survey

“…The expression of the late steps is developmentally regulated and vindoline production is related to aerial parts of the plant. The latest step in the biosynthesis is acetyl-CoA dependent, which makes a cell-free synthesis of vindoline [178] from tryptamine and secologanin unlikely [179].…”

“…4) was demonstrated [178,[180][181][182][183][184]. Endo et al [185] reported a cell-free production of 3',4'-anhydrovinblastine from vindoline and catharanthine with a maximum yield of 22% from the substrate.…”

The Coupling of Catharanthine and Vindoline to Form 3′,4′-Anhydrovinblastine by Haemoproteins and Haemin

“…Don] in low yields (grams per tonne of dry material) by lengthy extraction procedures (1) and for this reason attempts are now being made to produce them by other routes. The in vivo monomeric precursors of both dimers are believed to be catharanthine and vindoline (2,3,4) which are coupled in a condensation reaction to form an intermediate, 3…”

Stereoselective Conversion of Anhydrovinblastine into Vinblastine Utilizing an Anti-vinblastine Monoclonal Antibody as a Chiral Mould

“…[3][4][5][6][7] Many organic chemists have paid attention toward preparation of 7 from monomeric vindoline and catharanthine, both occurring as more plentiful constituents in the plant. [8][9][10][11][12][13][14] Langlois and Potier 15) found out that a dimeric alkaloid anhydrovinblastine (1) was transformed to 7 and its C-20Ј isomer, leurosidine (8), together with other diverse dimeric indole alkaloids including leurosine (4), though each in a 1-2% yield, by simple agitation of its organic solution under an air atmosphere. Based on the structural profile of the products, they proposed the synthetic pathway; the conjugated iminium intermediate 2 formed by air oxidation of 1 leads, through 1,4-addition of hydride or hydrogen atom from certain unoxidized alkaloid, to the enamine 3 which is the precursor of 7 and 8 (Chart 1).…”