While all of the products of the first five enzymes of the pathway in question are found in all plants as a requirement for protein formation the focus of this paper will be on secondary products. These are often found to be restricted to specific genera and which often have more obscure roles in the life of plants, although the indole phyto-hormones will also be considered.

1. Characteristics

For the purposes of this paper, the following hypothetical molecule will be considered as a "simple non-terpenoid indole alkaloid":



Figure 4: Representation of a typical "simple non-terpenoid indole alkaloid"

In this figure, all R-groups may be distinct, but generally will be fairly small, usually no more than four to five carbons in length and often containing no more than one or two heteroatoms. An example would be N,N-dimethyltryptamine (R1=R2=Me).

The following table shows some of the indole alkaloids, along with their R-groupings and occurrence where possible :

Table 2: Occurance and Characteristics of Some Simple Indole Alkaloids

Compound	Occurrence	R-Groups
Indole Glucosinolate	?	R1 – Glucose R3 - =NOSO3-K+
Gramine	Gramineae Phalaris arundinaceae Phalaris tuberosa Arundo donax	R8 – OH Nb1. Ethylamine chain of tryptamine base is shortened to methamine chain.
5-Methoxytryptamine	Cinchona ledgeriana	R8 – MeO
N,N-Dimethyltryptamine	Anandenanthera spp. Mimosa spp. Acacia polycantha Acacia nubica Acacia senegal Phalaris arundinaceae Phalaris tuberosa Arundo donax Mucuna pruriens Piptadenia spp. Virola spp.	R1 – Me R2 – Me
5-Methoxy-N,N-dimethyltryptamine	Virola spp. Anandenanthera spp. Phalaris arundinaceae Phalaris tuberosa Mucuna pruriens	R1 – Me R2 – Me R8 – MeO
5-Methoxy-N-methyltryptamine	Anandenanthera spp. Virola spp. Arundo donax	R1 – Me R8 – MeO
Psilocybin (4-Phosphoryl-N,N-dimethyltryptamine) Nb2. Not found in plants	Panaeolus spp. Psilocybe spp. Strophoria spp.	R1 – Me R2 – Me R7 – Phosphoryl
Psilocin (4-Hydroxy-N,N-dimethyltryptamine	Panaeolus spp. Psilocybe spp. Strophoria spp.	R1 – Me R2 – Me R7 – OH
Bufotenine (5-Hydroxy-N,N-dimethyltryptamine)	Anandenanthera spp. Piptadenia peregrina Arundo donax Mucuna pruriens Phalaris arundinaceae Phalaris tuberosa Ortica piluliferal	R1 – Me R2 – Me R8 – OH
Tryptamine	Barley Tomato Desmodium tiliaefolium Desmodium gangeticum Acacia baileyana Prosopis alba Prosopis nigra Burbea africana Piptadenia perigrina	All R – H
5-Hydroxytryptamine	Barley Tomato Griffonia simplicifolia Piptadenia peregrina Mucuna pruriens Musa sapientum Enlandia offinis Ortica piluliferal Ortica dioica Albizzia jubibrissin Phaseolus multiflorus Samanea saman Pisum sativum Passiflora quadrangularis Peganum harmala	R8 – OH
N-Acetyltryptamine	Prosopis nigra	R1 – Acetyl
5-Hydroxy-N-methyltryptamine	Piptadenia peregrina	R1 – Me R8 – OH
N-Methyltryptamine	Nectandra megapotamica	R1 – Me
6-Hydroxytryptamine	Peganum harmala	R9 – OH

2. Physiological/Chemical Ecological Uses

Secondary products were originally believed to play no role in plant physiology or ecological interactions, believing to be simply the result of the metabolic pressure of accumulation of primary products. The theory that these secondary products gave plants a selective advantage through protective devices and therefore developed as an evolutionary adaptation was suggested, the main failing being that it did not address compounds with seemingly little use or plants without much or any secondary metabolism. A third suggestion which tends to fall between these two is that the buildup of primary products did lead to new secondary products, which while they may not offer an advantage now, did at some point in the plants evolutionary history; plants which do not produce secondary products may simply have developed alternative modes of protection. This study supported the third theory indicating that few microorganisms produce alkaloids with pharmacological activity in animals, but do produce compounds with antibiotic and mycotoxic effects. Plants were similarly noted to create alkaloids with effects on organisms of a similar scale to themselves, animals and other plants, but had fewer compounds directed against microorganisms. Both examples pointed to fitness or evolutionary-based control of secondary metabolic production.

An extreme example of this chemical protection mechanism is in the glucosinolates, which are found in the vacuoles of some plants, and which include an indole form of glucosinolate. When plant tissue containing vacuoles with these compounds are damaged, the glucosinolates escape and are hydrolyzed into isothiocyanates, which have a toxic effect on most cells via alkylation reactions.

Scheme 11: Isothiocyanate production in damaged tissues through indole glucosinolate.

This mechanism, while effective does not really have anything to do with the indole nucleus itself, and a variety of other glucosinolates, which are just as effective exist. One mechanism of action often proposed specifically for the indole alkaloids is that of feeding deterrents, through foul taste or as species recognized poisons. Two well-researched examples of this are "phalaris staggers" noticed in grasses of the Phalaris genus and tryptamine’s effect on whitefly reproduction.

The toxic effect ("phalaris staggers") of Gramineae, as in the Phalaris genus noticed in ruminants such as sheep has been associated with their production of the indole alkaloids gramine, DMT, 5-MeO-DMT and bufotenine. Further studies on gramine in another Gramineae, barley lead to the finding that it could be found in especially high concentrations in the youngest leaves, where it had a negative effect on aphid population growth rates. Aphids of the species Rhopulosiphum padi L. and Schizaphis graminum were found to decrease their feeding behavior in the presence of higher concentrations of gramine in barley and were even found to have higher mortality rates when fed an artificial diet containing similar concentrations of gramine. Aphids known to feed off a variety of species were noted to choose low-alkaloid producing plants, while aphids with high species specificity were noted to ingest plants with higher levels of alkaloids, presumably as a modification which allows them to use the alkaloids in their own defense. This use of the plants secondary products goes one step beyond the typical evolution in parasitic organisms, that of formation of detoxification systems specific to the host organism.

To test the influence that tryptamine had on insect feeding and oviposition patterns, one study genetically transformed Nicotiana tabacum, a plant which does not normally contain the tryptophan decarboxylase enzyme, to produce tryptamine. Increased levels of tryptamine in these engineered plants were correlated with decreased whitefly pupae emergence and affected adult selection of leaves for feeding and oviposition in an inverse relationship.

Although Floss stated that it was difficult to generalize about the role that plant development plays in alkaloid biosynthesis, alkaloids found to have defensive characteristics are often found in the younger tissues of most plants as in these last two examples. Some alkaloids have been shown to be elicitable as well as developmentally regulated, such as in Camptotheca acuminata. In this species, tryptophan decarboxylase is regulated by two separate genes, one which appears to be expressed most often in young tissues, the second of which appears to only be expressed in tissues undergoing pathogen stress by fungal elicitors or methyl jasmonate (MeJa) stimulation.

The last role of indolous compounds considered here differs quite dramatically from that of the previous examples. It has been noted that some secondary products have a role in attraction of pollinators, and at least one example of this appears in the indole compounds, indole itself. In some of the Araceae during flowering, calorigen induces an increase in indole production at the same time as an increase in sensible heat in the male area of the flower. The combination of this increase in heat with the volatile nature of indole creates a smell which attracts insects and increases pollination rates.

3. Medicinal/Ethnobotanical Uses

The medicinal uses of the simple indole alkaloids are relatively few. While plants are known to produce innocuous compounds such as the neurotransmitter, serotonin, most other simple indole alkaloids have received infamous reputations. Many of the indole derivatives found in plants have been noted to have hallucinogenic activity in humans, including DMT, 5-MeO-DMT, bufotenine and possibly 5-MeO-NMT. Psilocin and psilocybin are examples of other indole alkaloids with pronounced psychedelic activity, but are found only in members of the fungi. A few other closely related indole alkaloids with hallucinogenic or psychedelic activity are the b -carbolines harmine and harmaline found in the Banisteriopsis genus, ibogaine found in the Tabernanthe genus and the ergolines. The ergolines, while commonly only known to occur in the fungus, Claviceps, also occurs in Ipomea species in the form of ergine or lysergic acid amide (LSA).

Figure 5: Structural Representation of Some of the Naturally Occurring Indole Hallucinogens

1. Characteristics

Most of the terpenoid indole alkaloid structures are based around that of strictosidine (Scheme 10) although in many cases this original structure is difficult to immediately see. For example, in the Aspidosperma and Hunteria type indole alkaloids, one cleavage and one new bond is formed in the main skeleton. In order to classify the vast number of alkaloids belonging to this class, a number of systems have arisen, however one of the simplest to follow is the system presented by P.M. Dewick, based on the original secologanin skeleton:

Scheme 11: Variation in the C₁₀ Skeleton Provided By Secologanin in the Indole Alkaloids

This diagram is rationalized through tracer studies indicating that each of the major types of alkaloids (Corynanthe, Aspidosperma and Iboga) derive their skeleton through cleavages of the original secologanin terpenoid precursor, followed by different reattachments of the lost carbons. Carbons with a hollow circle attached are occasionally cleaved in the final product, leaving nine of the original ten secologanin carbons.

2. Physiological/Chemical Ecological Uses

The terpenoid indole alkaloids have chemical ecological roles similar to those of the simple indole alkaloids. In Cinchona ledgeriana, alkaloid concentrations were found to be highest in the youngest portions of the plant, and as in studies with barley species, extracts of the plant fed to a parasite, Spodoptera exigua caused high mortality and detrimental growth patterns. After testing all the alkaloids found in the extracts, it was determined that the active alkaloids was the terpenoid indole alkaloid, cinchophyllene, the quinoline and 5-MeO-tryptamine alkaloids having no effect on either mortality or growth rates of Spodoptera exigua. As in studies of Cinchona ledgeriana, young tissues of Camptotheca acuminata were found to have the highest concentrations of TIAs, although in this plant the alkaloid levels could also be elicited through the effect of MeJa and yeast extracts on tdc transcript levels.

3. Medicinal/Ethnobotanical Uses

Scheme 12: Formation of Camptothecin from Tryptamine and Secologanin; Variation in the Basic Indole Skeleton

The formation of the main indole-based phytohormone, IAA proceeds through an amazing variety of pathways. In tomato and barley plants, two varieties of the pathway to IAA were determined, one starting with tryptophan through indole-3-pyruvic acid (IPA) to indole-3-acetaldehyde (IAld) and finally to IAA, the other starting with decarboxylation of trypophan to tryptamine, then through the common precursor IAld and on to IAA. While both plants used both paths in the formation of IAA, tomato plants were discovered to primarily use the IPA path, while barley used both paths equally. This dual pathway was supported in a study on tryptophan decarboxylase in Phalaris tuberosa.

Scheme 13: Tryptophan-Dependant Formation of Indole-3-Acetic Acid (IAA)

Non-tryptophan dependant pathways have also been suggested to occur, such as the formation of IAA from indole as demonstrated in maize. For the moment this pathway has not been confirmed, however it appears to occur through either InGP or indole itself, through a precursor, which has been identified as either indole-3-acetonitrile (IAN) or IPA.