Monoterpene-derived indole alkaloids

Subsequent Reactions of Strictosidine Classification and Structural Types of Indole Alkaloids Formation of the Major Indole Alkaloid Types Summary of Pathways Leading to Major Types of Monoterpene-Derived Indole Alkaloids Chemosystematic and Phylogenetic Application Monoterpenoid Indole Alkaloids of Pharmacologic Significance Vincamine... 

Although the majority of monoterpene-derived indole alkaloids occur in the Apocynaceae, Loganiaceae, and Rubia-... 

Many alkaloids contain an indole nucleus as a part of their structure. Monoterpene-derived indole alkaloids see Chapter 34) are the most important of these compounds, but several other significant types of indole alkaloids exist. Ergot alkaloids formed from tryptamine and a mevalonate-derived hemiterpene unit are of medical importance. Others, such as harmane alkaloids, physostigmine and a series of structurally similar alkaloids, Calycanthus alkaloids (Calycanthaceae) and related compounds (principally from the Rubiaceae), and relatively minor types of alkaloids from the Ascelpiada-... 

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

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. 

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 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. 

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... 

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... 

This is an example of a bicyclic ring system with the fusion of benzene and pyridine rings. Biosynthetically they are related to indole alkaloids since both groups are derived from the same two precursors, tryptophan and loganin—a monoterpene iridoid (Samuelsson 1992). 

Psychollatine is a monoterpene indole alkaloid, the major alkaloid from P. umbellata, being restricted to shoots (nearly 4% of dry weight in leaves). The alkaloid structure suggests an alternative biosynthetic pathway, STR-independent, by the condensation of tryptamine and a geniposide derivative [124],... 

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]. 

Wishing to provide a deeper understanding of the synthetic tactics, which are used on the examples that will follow, some general guidelines on the design of a common synthetic scaffold are provided. These guidelines follow David W.C. MacMillan s tryptophan-derived monoterpene indole alkaloids syntheses as an example [39] ... 

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... 

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