Terpenoid indole and related alkaloids

The terpenoid indole skeleton is the most widely found amongst the plant alkaloids, the number of known examples exceeding one thousand. As seen in e.g. ajmalicine 6.243) these alkaloids are constituted from a tryptamine unit (proved to derive from tryptophan and tryptamine [170]) and a C9 or Cjq unit which, after much experimentation, was proved to be terpenoid in origin. [Examination of 6.243) shows this is not immediately obvious.] 

Significant variation in the alkaloidal tryptamine fragment is associated with loss of one or both side-chain carbon atoms [see (6,272)] or transformation of the aromatic nucleus into that of a quinoline [see (6.275)], By far the greatest variation is associated with the terpenoid fragment. 

The appropriate incorporations of mevalonic acid (6.235) [as elsewhere in biosynthesis it is the (3-/ )-isomer which is utilized], and geraniol (6.236) and nerol (6.245) prove the essential correctness of the hypothesis the hydroxy-derivatives (6.246) and (6.247) were also utilized. Ensuing crucial experiments lay with identification of the cyclopentane monoterpene loganin (6.249) as a key intermediate in biosynthesis. Not only did (6.249) prove to be a specific alkaloid precursor, but its presence and biosynthesis from geraniol in Catharan-thus roseus, a plant used for most of the experiments, could be demonstrated [173, 174]. 

The most recent results [179, 180] have been obtained chiefly using enzyme preparations from plant tissue cultures, and they are most impressive allowing clear definition of the early stages of 

The Corynanthe alkaloids represented by ajmalicine 6.243) and tetrahydroalstonine (6.260) are the simplest variations of the stric- 

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The enzyme strictosidine synthase (EC 4.3.3.2) is responsible for the stereospecific coupling of tryptamine and secologanin, yielding strictosidine (Fig. 12). This glucoalkaloid is the precursor for all terpenoid indole and related alkaloids, including among others the Cinchona quinoline alkaloids. Hampp and Zenk (707) isolated and purified this enzyme to homogeneity from a cell suspension culture of R. serpentina. The enzyme could successfully be immobilized on CNBr-activated Sepharose 4B, as was reported for this enzyme isolated from Catharanthus roseus (102,708). It proved to be more stable than the C. roseus enzyme the half-life of the immobilized enzyme was 100 days at a temperature of 37°C. 

In the subsequent paragraphs some of the work in our laboratories in this field will be reviewed. It particularly involves the secondary metabolism in cell cultures of plants capable of producing terpenoid-indole and related alkaloids, i.e. Cinchona and Tabernaemontana. 

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