Monoterpene alkaloids iridoids

Many species of Castilleja (Scrophulariaceae) contain iri-doid monoterpenes (Arslanian et al, 1985) as well as pyrrol-izidine, quinolizidine, and monoterpene iridoid alkaloids (Stermitz et al., 1986a). Both pyrrolizidine and quinolizidine alkaloids appear to be taken from the hosts of these hemipar-asitic plants see Chapter 30). The larvae of Platyptilia pica (Pterophoridae) excrete but do not sequester iridoids. The adult moths contained rhexifoline, an iridoid monoterpene alkaloid (Stermitz et al, 1986a). 

Flowers of Penstemon whippleanus (Scrophulariaceae) serve as a host for the plume moth, Amblyptilia (Platyptilia) mica. These flowers contain (+ )-boschniakine (10) and other iridoid-monoterpene-derived alkaloids (McCoy and Stermitz, 1983). Another host of this moth, Castilleja rhexi-folia (Scrophulariaceae) contains rhexifoline (11), an iridoid monoterpene alkaloid, as the major alkaloid of the seeds and flowers. The moths and adults of the insect contain rhexifoline (Roby and Stermitz, 1984). Rhexifoline (11) also can arise in some instances from the presence of ammonia in workup from penstemonoside, but this possibility was specifically precluded in this study by use of bicarbonate in place of ammonia in the workup. 

The last review of the monoterpene alkaloids was published in this series in 1977 (i) and was based on the literature to the end of 1974. Since that time a substantial number of new monoterpene alkaloids have been isolated, new sources of established alkaloids have been identified, and several innovative syntheses of alkaloids in this series have been described. In addition, the in vitro formation of monoterpene alkaloids from iridoids has been pursued, including studies with human fecal flora, and some work... 

G. In Vitro Conversion of Iridoids and Secoiridoids to Monoterpene Alkaloids... 

Roby, M. R. and Stermitz, F. R. (1984) Penstemonoside and other iridoids from Castilleja rhexifolia. Conversion of penstemonoside to the pyridine monoterpene alkaloid rhexifoline J Nat Prod 47, 854-857. 

The principal groups of natural products belonging to this family of monoterpene derivatives are glycosidic and non-glycosidic iridoids ( see fig 1, refs 5-7 ), together with related compounds secoiridoids and bisiridoids, and monoterpene alkaloids ( see fig 2). 

CioH.jN, Mr 147.22, oil, bp. 100-103 °C(1 kPa),[a]i, -7.2° (CHCI3), a monoterpene alkaloid ( iridoids) from the east Asian creeper Actinidia polygama and other Actinidiaceae, Bignoniaceae, and Valerianaceae. It is a component of the defensive secretion of black beetles, ants, grasshoppers, and flies. Only the (5) enantiomer occurs in nature. A. exhibits antimicrobial properties and a deterrent effect against birds and arthropods , while cats are strongly attracted Synthesis There are various syntheses of the racemate and the unnatural (/I) enantiomer, but only three for the (5) enantiomer. The biosynthesis presumably proceeds from iridodial. 

Biosynthesis In plants the quinoline system can be formed by several different biogenetic routes (biochemical convergence). In the Cinchona alkaloids tryptophan acts as the precursor while simple quinolines, furoquinolines, and acridines originate from an-thranilic acid. The second biosynthetic parmer is often a hemiterpene (for furoquinolines) or an iridoid monoterpene (secologanin, see secoiridoids) for 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). 

Loganin (6) is a key intermediate in the biosynthetic pathway leading to other iridoid monoterpenes as well as complex indole alkaloids. Many of these additional compounds are derived by conversion of this bicyclic iridoid monoter-pene into secologanin (18). The mechanism by which ring cleavage occurs to yield secologanin is not well understood, but apparently the cleavage happens after oxidation of the... 

Bate-Smith et al., 1975), whereas there does not appear to be a close relationship of the Comaceae to the Apiaceae (Umbelliferae) and the Araliaceae with which they are placed by many phylogenists. The Apiaceae and Araliaceae completely lack iridoid compounds. The presence of alkaloids in the Icacinaceae and the Nyssaceae based on an iridoid monoterpene structure suggests that these plants also may be related to the Comaceae. 

The order Gentianales (Apocynaceae, Gentianaceae, Lo-ganiaceae, Rubiaceae, and Theligonaceae) contains normal iridoid monoterpenes and secoiridoids, as well as iridoid-derived alkaloids in families other than the Asclepiadaceae. Multiple types of alkaloids are found in the Apocynaceae (indole and steroidal types), the Loganiaceae, and Rubiaceae (emetine, quinine, and indole types). 

The stems and leaves of Castilleja rhexifolia (Scrophula-riaceae) contain senecionine (5) and its A -oxide (obtained from Senecio triangularis) as their main alkaloids. The major alkaloid of the blossoms and seeds is rhexifoline, an iridoid-monoterpene-derived alkaloid, which is found in many Castilleja species. These plants serve as a host for the plume moth, Platyptilia pica. The larvae primarily eat the green seeds. Both the larvae and the adults of this insect contain rhexifoline (Roby and Stermitz, 1984). Plants of C. hispida contain quinolizidine alkaloids, and occasional plants of C. sulphurea contain quinolizidine alkaloids, whereas those of C. occidentalis do not contain alkaloids other than rhexifoline. The iridoid monoterpene content of all these alkaloids is similar. The larvae were found to excrete the monoterpene iridoids (Stermitz et al., 1986). 

Loganin is an iridoid glucoside which occupies a central position in the biosynthesis of Corynanthe, Aspidosperma, Iboga, Ipecacuanha, Cinchona, and structurally simpler monoterpene alkaloids. For a review of the extensive researches that led to confirmation of the key role of loganin in alkaloid biosynthesis, see A. R. Battersby, Biochem. Soc. Symp., 29, 157 (1970) A. R. Battersby, Chem. Soc. Spec. Period. Rep., 1, 31 (1971) A. I. Scott, Accts. Chem. Res., 3, 151 (1970). For a useful account of the chemistry of iridoid glucosides see, J. M. Bobbitt and K. -P. Segebarth in Cyclopentanoid terpene Derivatives, Eds., W. I. Taylor and A. R. Battersby, Marcel Dekker, New York, 1969, p 1. 

The CNS-depressant component of valerian is still unknown. Thus far, three major constituents of valerian have been identified the volatile or essential oil, containing sesquiterpenes and monoterpenes, nonglycosidic iridoid esters (valepotriates), and a small number of alkaloids (2). Valepotriates are unstable compounds and are easily hydrolyzed by heat and moisture (22). In addition, valepotriates are not water soluble, and aqueous extracts contain... 

Iridoids are derivatives of monoterpenes and occur usually, but not invariably, as glycosides.100,101 Structurally, they are cyclopentano [r] pyran monoterpenoids and they provide a biogenetical and chemotaxonomical link between terpenes and alkaloids. The cleavage of the cyclopentane ring of iridoids produces secoiridoids.10... 

The CNS depressant component of valerian is still unknown. Thus far, three major constituents of valerian have been identified the volatile or essential oil, containing sesquiterpenes and monoterpenes, nonglycosidic iridoid esters (valepotriates), and a small number of alkaloids (Anonymous, 1991). Valepotriates are unstable compounds and are easily hydrolyzed by heat and moisture (Wagner et al., 1998). In addition, valepotriates are not water soluble, and aqueous extracts contain small amounts (Wagner et al., 1998). For example, the aqueous extract used in the study by Balderer and Borbely, described previously, was analyzed using thin-layer chromatography (TLC), and no valepotriates were detectable. Furthermore, valepotriates are not well absorbed orally (Tyler, 1993). Therefore, the likelihood that valepotriates are a major contributor to valerian s effects is questionable. Because of the low amount of alkaloid present in preparations, their contribution is also questionable (Houghton,... 

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