Strictosidine lactam

The 200GW line proved to be quite different, and of particular interest was the discovery that this line produced catharanthine (4) at levels about three times that of the intact plant (0.005%) (155,159,160). Curiously, the predominant alkaloid (60.48%) was strictosidine lactam (41), which is not normally seen in extracts of intact plants. Variation of the pH and added phytohormones did not significantly alter the pattern of alkaloids produced by this cell line (160). Further cell line studies (161) afforded one line (176G) which produced mainly ajmalicine (39) and lochnericine (73) and one (299Y) which apparently contained relatively inactive p-glucosi-dases, since the major alkaloids produced were strictosidine (33) (83%) and strictosidine lactam (41) (Table XIII). 

It is reasonable to assume that the unique precursor of angustine bases is strictosidine lactam (16), the intramolecular cyclization product of strictosidine (17). The prerequisite for cyclization is the presence of a secondary amino group in the C ring of strictosidine, that is to say, the presence of a hydrogen atom on N-4. Indeed, compound 18, the AT-benzyl-substituted aglycone of strictosidine, is not subject to cyclization, but is rather in equilibrium with the open form (19) (27). Similarly, replacement of a tetrahydro-(3-carboline unit, such as one finds in strictosidine, by a P-carboline moiety inhibits the cyclization step and thus leads to tetracyclic derivatives, typical of the alkaloids of the genus Pauridiantha. 

In summary, strictosidine (17) is likely to be the unique precursor of angustine bases (15) on the one hand and of alkaloids 7 to 13 on the other. The alternative pathway which produces cyclization to strictosidine lactam, namely, aromatiza-tion of the C ring, should most probably occur at an early stage of the biosynthetic route to the indole alkaloids of Pauridiantha. 

STRICTOSIDINE Lactam Type Naucleae and Logan iaceae... 

Ajmalicine and vallesiachotamine are amongst the alkaloids produced by cultures of cell lines 943,426 953,426 and 200 GW of Catharanthus roseus ia the first two of these cell lines also produced yohimbine and isositsirikine, while cell lines 953 and 200 GW also produced strictosidine lactam. 

The difference in stability of vincoside and strictosidine as the free bases was quite marked. Aqueous sodium carbonate at room temperature rapidly converted the former into vincoside lactam (50 or 52) mp 201-202° [a]D-118° (MeOH), whereas the latter remains unaffected. In order to obtain strictosidine lactam (strictosamide) (50 or 52) [a]D - 75° (MeOH) it was found necessary to heat the reaction mixture at 70° for a considerably longer time. Since then, both these transformation products have been isolated from natural sources—vincoside lactam from A. rubescens (9) and strictosidine lactam from R. stricta (24) and N. latifolia (3). One notable difference between the epimers was that strictosidine lactam tetraacetate (51 or 53) displayed one acetate signal in its NMR spectrum at anomalously high field (t8.78), a characteristic not shared by the vincoside derivative. 

Eilert et al. (714) identified strictosidine lactam as the main alkaloid produced in two cell lines of V. major cv. variegata. The high yielding cell line produced 0.5-1 mg/g dry weight. Transferring the cells to an alkaloid production medium resulted in a 6- to 8-fold increase in alkaloid levels combined with greening of the cells. 

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