Monoterpene alkaloids derivatives

Fu JJ, Qin JJ, Zeng Q, Huang Y, Zhang WD, Jin HZ (2011) Two new monoterpene alkaloid derivatives from the roots of Incarvillea arguta. Arch Pharm Res 34 199-202... 

Scheme 4.6 The common core structure of many indole monoterpene alkaloids might be accessed through a tetracyclic Zincke aldehyde-derived building block...

We became particularly interested in strychnine when we noticed that the tetracycle 21 (Scheme 4.6), which might be readily available by an intramolecular Diels-Alder cycloaddition of a tryptamine-derived aminodiene, contains much of the complexity of this popular alkaloid target. In fact, this tetracycle is common to many indole monoterpene alkaloids including members of the Strychnos, Aspidosperma, and... 

Chapter 3 by Fujii and Ohba reviews the progress that has been made since 1983 on the ipecac alkaloids and related bases. In particular, the very substantial progress made in the isolation of more polar alkaloids lacking the methyl groups of the well-established alkaloids and the tetrahydroiso-quinoline monoterpene glucoside derivatives is discussed. In addition, there has been substantial progress in developing new and innovative synthetic procedures for both the established and the new alkaloids. 

When antirrhinoside (318) was reacted under the standard conditions, the dihydroxy acetate monoterpene pyridine alkaloid derivative 319 was produced cleanly in about 10% yield (224). The structure was deduced spectroscopically. An acetate group was apparent (8h 2.1 Sc 21.9,172.6) and doublets (J = 5.6 Hz) at 4.31 and 5.11 ppm. The latter showed an NOE with H-4 and was therefore assigned to H-6. X-ray crystallography affirmed the acetate group to be located at C-8 and defined the stereochemistry of C-6 and C-7 to be as shown in 319. 

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). 

Ch. 2 Alkaloids Derived from Tiyptamine and an Unrearranged Monoterpene Unit Ch. 3 The Corynantheine-Heteroyohimbine Group Ch. 4 The Yohimbine Group... 

The parent compound of the secoiridoids is secologa-nin (see secoiridoids), the most important intermediate in the biogenesis of alkaloids that are not derived from an amino acid. This includes most indole alkaloids, the ipecac, the Cinchona, and the pyrroloquinoline alkaloids as well as simple monoterpene alkaloids The best known biological property of the I. is their bitter taste. However, bitter principles are mostly not used as pure substances, instead alcoholic extracts are preferred to stimulate appetite (increased secretion of gastric juice). Furthermore, bitter substances are used to modify the taste of pharmaceutical products. Some I. exert various effects on the central nervous system as a consequence of their volatility and lipophilicity, e.g., nepetalactone, iridodial, teucrium lactones, and valepotriates. 

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. 

Tryptophan-Derived Indole and Indole Monoterpene Alkaloids As for alkaloids derived from tyrosine and phenylalanine, those derived from tryptophan are formed after decarboxylation of the amino acid (into tryptamine) and possible hydroxylation of the aromatic carbocycle (e.g., serotonin) and N-methylation (e.g., psilocin). As previously, tryptamine can also react through Pictet-Spengler reactions to form tetrahydro-p-carbolines, which can be aromatized, for example, into harmine (Scheme 1.8) [16]. 

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. 

Thomas (23) predicted that the non-tryptamine moiety of the indole alkaloids is derived from a cyclopentanoid monoterpene precursor. Wenkert (2k) independently reached to the same conclusion. 

Among the alkaloids, the most unusual example is an acaricidal (lethal to arachnids) monot-erpene derivative, altemicidin (Structure 18.3). This novel alkaloid was purified from amarine strain of Streptomyces sioyaensis SA-1758 isolated from marine sediments collected from the northern part of Japan. It yielded potent antitumor activity in vitro against L1210 murine leukemia and IMC carcinoma cell lines, but was toxic in vivo in mice. Altemicidin is a novel sulfur- and nitrogen-containing microbial metabolite with a monoterpene carbon skeleton.12... 

Stereospecific condensation between tiyptamine and seco-loganin in a Mannich-like reaction is carried out by the enz)une (S)-strictosidine s)m-thase and results in the formation of the glucoalkaloid, (S)-strictosidine, from which most monoterpene indole alkaloids are derived (Figs. 2.1 and 2.9). 

Buriat, V., Oudin, A., Courtois, M., Rideau, M. and St. Pierre, B. (2004) Co-expression of three MEP pathway genes and geraniol-lO-hydroxylase in internal phloem parenchyma of Catharanthus roseus implicates multicellular location of intermediates during the biosynthesis of monoterpene indole alkaloids and isoprenoid-derived primary metabolites. Plant., 38,131 1. 

The isoquinoline alkaloids are the second largest group of alkaloids, numbering about 6000, and can be viewed as five subgroups—the simple tetrahydroisoquinolines, the benzylisoquinolines, the phenethylisoquinolines, the Amaryllidaceae alkaloids, and the monoterpene isoquinolines. In addition, there are a number of simple phenethylamine derivatives, including ephedrine (originally from Ephedra species, but now synthesized) and pseudoephedrine, used for asthma and nasal... 

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