Guettarda Alkaloids

Cathenamine (20, 21-dihydroajmalicine) and 4,21-dehydrogeissoschizine have been isolated from the leaves of Guettarda eximia (71, 86). 

Cathenamine and 4,21-dehydrogeissoschizine have both been demonstrated to be the central intermediates in the enzymatic production of heteroyohimbine-type alkaloids - ajmalicine, 19-epiajmalicine, and tetrahydroalsonine (128, 152) (Fig. 

21-Dehydrogeissoschizine was also converted into geissoschizine by chemical and enzymatic reductions. 

Recently, guettardine was obtained from the bark of Guettarda heterosepala in a 0.025% yield (17). This alkaloid can be considered to be an intermediate between the corynanthe and the cinchonamine-type alkaloids that are precursors and congeners of quinine (Fig. 5.2.20). 

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Kan-Fan and Husson reported the isolation and structure elucidation of 4,21-dehydrogeissoschizine chloride (32) from the leaves of Guettarda eximia (39). It has been suggested that this alkaloid is a biosynthetic intermediate of several... 

Cathenamine (100) has been identified as an early intermediate in terpenoid indole alkaloid biosynthesis (cf. Vol. 8, p. 27). It has also been isolated from Guettarda eximia. Another alkaloid, 4,21-dehydrogeissoschizine (99), has now been isolated from this plant it is readily converted into (100) in alkaline solution.29 On incubation with an enzyme preparation from Catharanthus roseus cell cultures in the presence of NADPH at pH 7, (99) was converted into ajmalicine (102), 19-ep/-ajmalicine (103), and tetrahydroalstonine (104), which are the normal products with this enzyme preparation. In the absence of NADPH, cathenamine (100) accumulated.30 The reaction to give (100) proceeded linearly with time, and was dependent on the concentration of protein and substrate. No conversion occurred in the absence of enzyme. 

However, only the E-alkene (78) has been isolated from Guettarda eximia, and the related alkaloids geissoschizine and the isosit-... 

A new alkaloid (100), related to cathenamine (82), has been isolated from Guettarda eximia. It is readily converted chemically into cathenamine (82), presumably via (81). It seems likely that (100) has a biosynthetic role, and it may be that access to alkaloids with different stereochemistries at C-19 and C-20 occurs via (81) (100). ° ... 

C21H22N2O3, Mr 350.42, amorphous, [a]D -52° (CHCI3). 0 unstable, reactive alkaloid, existing as /d -immonium salts, isolated from Guettarda exi-mia (Rubiaceae) and synthesized enzymatically with enzymes from Catharanthus roseus cell suspension cultures C. plays a key role in the biosynthesis of monoterpenoid indole alkaloids, e.g., the hetero-yohimbine alkaloids such as ajmalicine, 19-epi-aj-malicine, and tetrahydroalstonine (see Alstonia alkaloids). 

The structure of guettardine (72), isolated from Guettarda heterosepala, suggests that this alkaloid may represent an intermediate between the Corynanthe and cinchonamine types of alkaloids (Herbert, 1986). If so, cleavage of the p-carboline system must precede the formation of the quin-uclidine ring (Fig. 34.20) (Herbert, 1986). 

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