Iridoid indole alkaloids

Several natural products such as cannabinoids, iridoids, indole alkaloids,fiirofuran lig-nans and other compounds have been synthesized using this methodology. Deoxyloganin (210) was obtained by condensation of the enantiomerically pure aldehyde (208) with Meldrum s acid in the presence of ethylenediammonium diacetate to give the Knoevenagel product (209), which cyclizes immediately, yielding the cycloadducts (211) and (212) in a 10 1 ratio (Scheme 40). (-)-Ajmalicine... 

Carboline Pyrrolidinoindole Ergoline Iridoid indole alkaloids Harman alklaoids Physostigmine Ergot alkaloids Alkaloids of Rauwolfia, Calabash curare. Vinca, Strychnos and Cinchona... 

Vinca alkaloids, Catharanthus alkaloids a group of about 60 iridoid indole alkaloids from Vinca (Catharanthus) spp. Structurally, they are tetra- or penta-cyclic indole derivatives with an iridoid component, e g. vindoline, [a]n -18° (CHCI3), m.p. 174-176°C, and vincamine, [ci]d + 41° (pyridine), m.p. 232-233 °C. These are accompanied in the leaves by small quantities (about 0.005%) of two dimeric V.a., i.e. Vinblastine (see) and fincristine (see) (Hg.). Tryptophan and mevalonic acid are biosynthetic precursors... 

Mannich condensations may proceed spontaneously even under physiological conditions, i.e., at room temperature, physiological pH, etc., but may also be enzyme catalyzed. In vivo aldehydes or x-keto acids act as carbonyl compounds. Typical Mannich condensations occur in the formation of the iridoid indole alkaloids (D 21.3) and the isoquinolines (D 22.1.2). 

B, Iridoid Indole Alkaloids. Most jS-carbolines are derived from tryptamine and the iridoid secologanin (D 6.1.2). In dependence on the structure of the iridoid part alkaloids of the Corynanthe-Strychnos type as well as of the Aspidosperma and Iboga types may be distinguished. The latter are formed by rearrangement of the iridoid part which is shown schematically in Fig. 259 and in detail in Fig. 261. 

A key intermediate in the biosynthesis of all iridoid indole alkaloids is the glu-coside strictosidine (isovincoside. Fig. 260). Strictosidine is transformed to aj-malicine, which is a precursor of stemmadenine, tabersonine, vindoline and catharanthine (Fig. 261). The dimeric alkaloids, like vinblastine (vincaleuco-blastine) and vincristine (Fig. 259) are derived from monomeric precursors, e.g. catharanthine and vindoline. 

Of biochemical interest is the presence of quite significant amounts (up to 5%) of the iridoid glycoside loganin (see page 188) in the fruit pulp of Strychnos nux-vomica. This compound is, of course, an intermediate in the biosynthesis of strychnine and other terpenoid indole alkaloids. 

Geraniol 10 hydroxylase catalyzes the the cytochrome P450 dependent hydroxylation of geraniol at the C-10 position to commit this substrate to the formation of iridoid monoterpenoids (Fig. 8.2). In Catharanthus roseus, this intermediate is converted to secologanin for producing the tryptamine containing monoterpenoid indole alkaloids characteristic of this plant. 

All terpenoid indole alkaloids are derived from tryptophan and the iridoid terpene secologanin (Fig. 2b). Tryptophan decarboxylase, a pyridoxal-dependent enzyme, converts tryptophan to tryptamine (62, 63). The enzyme strictosidine synthase catalyzes a stereoselective Pictet-Spengler condensation between tryptamine and secologanin to yield strictosidine. Strictosidine synthase (64) has been cloned from the plants C. roseus (65), Rauwolfla serpentine (66), and, recently, Ophiorrhiza pumila (67). A crystal structure of strictosidine synthase from R. serpentina has been reported (68, 69), and the substrate specificity of the enzyme can be modulated (70). 

BIOGENESIS OF ANTHRAQUINONES, IRIDOIDS AND INDOLE ALKALOIDS FOUND IN HEDYOTIS... 

Loganin is the intermediate that undergoes the ring opening reaction which leads to the formation of secoiridoids. This step occurs by a mechanism that remains to be elucidated and affords secologanin (31) as the precursor of all of the secoiridoids and consequently, of the indole alkaloids that incorporate this pattern [1, 2, 3]. General biosynthesis of iridoids is given in fig. 1. 

Isoprenoids (isopentenoids). The name for a group of natural products made up of isoprene units (e.g., ses-qui-, di-, and triterpenes, iridoids, carotinoids, steroids, natural rubber, etc.). Many non-isoprenoid compounds, however, do possess isoprenoid side chains, e.g., tocopherols, ubiquinones, chlorophyll, or contain isoprenoid structures incorporated into their skeletons, e.g., monoterpenoid indole alkaloids, penitrems, Cinchona alkaloids. 

Formation of Deoxyloganic Acid from Geraniol Formation of 8-e/ i-Deoxyloganin and Related Iridoids Iridoids Derived from 10-Hydroxycitronellol Conversion of Loganin to Secologanin Secologanin as a Precursor for Indole Alkaloids Distribution of Iridoid Monoterpenes Biological Activity... 

Monoterpene and indole alkaloids are frequently derived from iridoid monoterpene precursors (Inouye, 1991). 

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