Indole alkaloids, simple

L-tryptophan Indole alkaloids Indole Simple indole Arundacine... 

This structural group of indole alkaloids covers simple indole alkaloids (e.g., tryptamine, serotonin, psilocin and psilocybin), /3-carboline alkaloids (e.g., harmine), terpenoid indole (e.g., ajmalicine, catharanthine and tabersonine), quinoline alkaloids (e.g., quinine, quinidine and cinchonidine), pyrroloindole... 

Simple indole alkaloids 8, 111, 112, 113 Simple phenylamine alkaloids 110 Simple tetrahydroisoquinoline alkaloids 7,... 

Although the natural occurrence of indole and the biosynthesis of the indole ring system are of importance and relevance to the wider question of the biosynthesis of the complex indole alkaloids, indole will not be discussed in detail here, as it is not an alkaloid. For a comprehensive and critical account of the occurrence of indole and its simple derivatives in plants, the reader is referred to the article by Stowe (8). 

Chapter 17. Terpenoid indole alkaloids and simple indole alkaloids. . . 155... 

TERPENOID INDOLE ALKALOIDS AND SIMPLE INDOLE ALKALOIDS... 

EXPERIMENTAL CONDITIONS USED FOR GAS CHROMATOGRAPHY OF TERPENOID INDOLE ALKALOIDS AND SIMPLE INDOLE ALKALOIDS... 

Physostigmine from the Calabar bean Physostigma venenosum (Fig. 130) is an indole alkaloid of simple structure. It is derived from tryptophan via its biogenic amine, tryptamine. 

Hi) Dehydrogenation. j3-Carboline derivatives may be obtained from tetrahydro-)3-carbohnes by zinc dust distillation or high temperatmre dehydrogenation with selenium or palladium black. Many of the complex indole alkaloids may be degraded, with bond cleavage, to yield simple )3-carbolines under these conditions and this approach has become a standard method in structural elucidations. Examples are numerous but outside the scope of this review. 

The most likely explanation for these results is that simple phenolics inhibit a very large array of enzymes in vitro. The most likely explanation for the CNS effects of Uncaria rynchophylla would be that indole alkaloids, such as dihydrocorynanteine or hirsutine (32), interact with the central neurotransmission and possibly the serotonin ergic system. 

A fourfold anionic domino process consistingofadominoMichael/aldol/Michael/ aldol process was used by Koo and coworkers for the synthesis of bicyclo[3.3.1]non-anes. They employed 2 equiv. of inexpensive ethyl acetoacetate and 1 equiv. of a simple a, 3-unsaturated aldehyde [290]. Differently substituted dihydroquinolines were assembled in a Michael/aldol/elimination/Friedel-Crafts-type alkylation protocol by the Wessel group [291]. An impressive approach in this field, namely the construction of the indole moiety 2-557, which represents the middle core of the man-zamines, has been published by Marko and coworkers [292]. Manzamine A (2-555) and B (2-556) are members of this unique family of indole alkaloids which were isolated from sponges of the genus Haliclona and Pelina (Scheme 2.126) [293]. 

The described approach also allows a simple access to indole alkaloids of the vallesiachotamine type. In this process, the Cbz-protected secondary amino function in the formed cycloadducts such as ent-2-805 is deprotected by hydrogenolysis. There follows an attack at the lactone moiety to form a lactam. In this way, the indole alkaloid (-)-dihydroantirhin (2-797) was prepared [400, 401]. 

The intramolecular Pummerer reaction has been applied to the synthesis of simple quinolizidine alkaloids like lupinine <2000JOC2368>, and also to arenoquinolizine alkaloids. Thus, the 2-(2-piperidyl)indole 284 was converted to indolo[2,3- ]quinolizidine 287 following a protocol that has as the key step the regioselective cyclization onto the indole 3-position of a thionium ion generated by Pummerer reaction from the appropriately substituted compound... 

A simple method was developed for the cleavage of the C-2—C-3 bond of indole alkaloids by the use of formic acid-formamide as reagent. Thus 2,3-seco derivatives of yohimbine (74), hirsutine (58), and reserpine (109) were prepared... 

Cryptopine-type indole alkaloid bumamicine (572) has been synthesized from geissoschizine methyl ether (31) (287). In the first step, geissoschizol (34) was prepared, and then cleavage of the C/D ring fusion was carried out by means of ethyl chloroformate. Finally, C-3 carbonyl and 7V-methyl groups were developed by simple oxidation, reduction, and repeated oxidation steps. 

Buchwald parlayed the powerful Buchwald-Hartwig aryl amination technology [439-447] into a simple and versatile indoline synthesis [448-452], For example, indole 368, which has been employed in total syntheses of the marine alkaloids makaluvamine C and damirones A and B, was readily forged via the Pd-mediated cyclization shown below [448], This intramolecular amination is applicable to the synthesis of -substituted optically active indolines [450], and o-bromobenzylic bromides can be utilized in this methodology, as illustrated for the preparation of 369 [451]. Furthermore, this Pd-catalyzed amination reaction has been applied to the synthesis of arylhydrazones, which are substrates for the Fischer indole synthesis [453,454],... 

When propargylamine 183 was subjected to a homologative allenylation (Crabbe reaction) at 100 °C, the resulting allene underwent a spontaneous Diels-Alder reaction to give the adduct 184. This intramolecular cycloaddition-oxidation sequence provided a simple route to indole alkaloids such as hippadine and ds-trikentrin B [148]. 

Blind snakes find their prey by using the prey s pheromones. The wormlike Texas blind snake, Leptotyphlops dulcis, of the southwestern United States leads a subterranean life and feeds on termites and ant brood. It finds ants by following their pheromone trails (Gehlbach etal, 1968). Other blind snakes such as the American blindsnake, Typhlops pusillus (Gehlbach et al, 1971), and the Australian blindsnake, Ramphotyphlops nigrescens (Webb and Shine, 1992), also follow odor trails of ants, their prey. Texas blind snakes are attracted to the simple alkaloid skatole (methyl indole Fig. 12.4), an amine with an unpleasant odor from the ant Neivamyrmex sp. (Watkins etal, 1969). 

A new benzannulation methodology was developed in order to overcome the limitations of electrocyclic ring closure of divinylindoles. The cyclization is achieved via an allene-mediated electrocyclic reaction of 2,3-difunctionalized indoles. This method is more efficient for the synthesis of highly substituted 2-methyl carbazole alkaloids (559). The 3-alkenyl-2-propargylindole 557, a precursor for the allene intermediate, was prepared from 2-formylindole over several steps using simple functional group transformations (536,537) (Scheme 5.20). 

The a for structural development of serotonin (simple indole alkaloid) is L-tryptophan, and the j3 is 5-hydroxy-L-tryptophan (Figure 64). Serotonin is a monoamine. It is a hioactive alkaloid known as a neurotransmitter. It has been found in the cardiovascular system, in Wood cells and the peripheral and CNS. 

Figure 64. Structural development of simple indole alkaloids.

Hibino, S. and Choshi, T. 2001. Simple indole alkaloids and those with a nonrear-ranged monoterpenoid unit. Nature Product Reports, 18 66-87. 

EXTENSIONS AND COMMENTARY N-Methyltryptamine (monomethyltryptamine, NMT) is an alkaloid that has been found in the bark, shoots and leaves of several species of Virola, Acacia and Mimosa. However, the major snuffs associated with these plant have been shown to also contain 5-MeO-DMT and are discussed there. NMT has been synthesized in a number of ways. One can react 3-(2-bromoethyl)indole with methylamine. NMT can be isolated as the benzoyl derivative from the methylation of tryptamine with methyl iodide followed by reaction with benzoyl chloride, with the hydrolysis of this amide with alcoholic KOH. It can also be synthesized from indole with oxalyl chloride, with the resulting glyoxyl chloride reacting with methylamine in ether to give indol-3-yl N-methylglyoxalylamide (mp 223-224 °C from IPA) which is obtained in a 68% yield, which is reduced to NMT to give the amine hydrochloride (mp 175-177 °C from ) in a 75% yield. The most simple and direct synthesis is the formamide reduction given above. 

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