Secologanine

Yohimbine (104), also from the bark of C.johimbe K Schum. and from the roots of R. serpentina (1. ) Benth. has a folk history (unsubstantiated) of use as an aphrodisiac. Its use has been confirmed experimentally as a local anesthetic, with occasional employment for rehef ia angiaa pectoris and arteriosclerosis, but is frequently contraindicated by its undesired renal effects. Yohimbine and some of its derivatives have been reported as hahuciaogenic (70). In addition, its pattern of pharmacological activities ia a variety of animal models is so broad that its general use is avoided. All ten carbon atoms of secologanin (102) as well as the entire skeleton of tryptamine (98, R = H) are clearly seen as iatact portions of this alkaloid. 

After the stmcture and absolute stereochemistry of cleavamine (111), C22H24N2, was estabUshed, its synthesis was shortly completed and impetus to unravel the stmcture of the dimeric bases (22) was bolstered (77). Again, the fragment, now only slightly modified from that originally present in secologanin (102), is readily seen in catharanthine (107). 

Iridoids and their related alkaloids are widely spread in angiosperms and are found in 13 orders and 70 families including Rutales, Buxales, Hamamelidales, Comales, Loasales, Gentianales, etc. Important iridoids are loganin, found in high amounts in Strychnos nux-vomica and in Catharanthus roseus, and secologanin found especially in Caprifoliaceae. 

Contin, A. et al.. The iridoid glucoside secologanin is derived from the novel triose phosphate/pyruvate pathway in a Catharantus roseus cell culture, FEES Lett., 434, 413, 1998. 

Indole alkaloids from Tabernaemontana plants are all biogenetically derived from tryptophan (tryptamine) and secologanine, which constitute the indole and terpenic portions, respectively, and can be classified into nine main types depending on the structural characteristics of their skeleton (Fig. 1). 

A few alkaloids, clearly originating from tryptophan and secologanine, cannot be accomodated in the previous types. They form the group of miscellaneous monomeric alkaloids. 

The work by Scott and Lee 165) on the isolation of a crude enzyme system from a callus tissue culture of C. roseus was followed by studies of Zenk et al. on an enzyme preparation from a cell suspension system which produced indole alkaloids 166). The cell-free preparation was incubated with tryptamine and secologanin (34) in the presence of NADPH to afford ajmalicine (39), 19-epiajmalicine (92), and tetrahydroalstonine (55) in the ratio 1 2 0.5. No geissoschizine (35) was detected. In the absence of NADPH, an intermediate accumulated which could be reduced with a crude homogenate of C. roseus cells in the presence of NADPH to ajmalicine (39). Thus, the reaction for the formation of ajmalicine is critically dependent on the availability of a reduced pyridine nucleotide. 

In 1978, Kutney and co-workers reported on the preparation of cell-free extracts from mature C. roseus plants which produced vindoline (3) (169). Leaves from the plants were homogenized in buffer in the presence of Polyclar AT, and the supernatant produced by centrifugation at 30,000 g was incubated with [2- C]tryptamine and secologanin for 2 hr at 34°C in the presence of FAD and NADPH. Vindoline (3) was isolated by TLC, diluted with cold material, and recrystallized to constant activity. Incorporations were in the range 1.10-1.36%, and no incorporation was observed when boiled enzyme preparation was used. Stemmadenine (36) was not incorporated into vindoline (3) using this preparation. These dramatic results were subsequently published in full (170). 

The enzyme responsible for the stereospecific condensation of trypt-amine and secologanin 34) was called strictosidine synthase, and its presence was demonstrated by Treimer and Zenk 194) in a number of indole alkaloid-producing plants, including Amsonia salicifolia, Catharanthus roseus, Ochrosia elliptica, Rauwolfia vomitoria, Rhazya orientalis, Stem-madenia tomentosa. Vinca minor, and Voacanga africana. Enzyme activity as high as 1698 pkat/mg protein was observed for O. elliptica. No... 

From dopamine, the pathway of tetrahydroisoquinoline alkaloids, such as emetine and cephaeline (Figure 37), also begins. Dopamine and secologanin undergo a Mannich-like to produce A-deacetylisoipecoside and ipecoside, and after hydrolysis and transformation, this is converted to emetine and cephaeline. 

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