Carbolines biosynthesis

Thus th,e biosynthesis of anhalonidine (12) involves condensation of pymvic acid with (7) to give (8) which then leads on to the alkaloid. A similar pathway is adduced for anhalamine (13), where glyoxylic acid replaces pyruvic acid (Kapadia et al. 1970). We have found in a case with some parallels that the /3-carboline alkaloids, harman (17) and eleagnine (16) are biosynthesized via the naturally occuring amino-acid (14) (15) is also implicated as an intermediate (Herbert and Mann 1982) (Fig. 2). We are currently examining the chirality of precursor (14) as a final test of its intermediacy in jS-carboline biosynthesis. 

Bischler-Napieralski reactions, 4, 279 carboline synthesis from, 4, 516 Mannich-type reactions, 4, 279 sulfur isosteres, biological activity, 4, 913 synthesis, 4, 337, 913 Tryptophan biosynthesis, 1, 264 carboline synthesis from, 4, 516 molecular structure, 4, 162 Tryptophan hydroxylase in serotonin biosynthesis, 1, 261 Tryptophan oxygenase... 

Brevicolline.—The /3-carboline part of the plant alkaloid brevicolline (114) has been shown to derive from tryptophan (94) and pyruvic acid.37 Putrescine (4) and related compounds provide the pyrrolidine ring.38 A key intermediate in brevicolline biosynthesis is likely to be (113), derived by oxidative decarboxylation of (111), which in turn is formed through the condensation of (94) with pyruvic acid condensation of (113) and (112) (formed from putrescine) would lead to (114). This has been supported by successfully mimicking the biogenetic sequence, starting with the chemical oxidative decarboxylation of (111).39... 

Of the more than 4500 known naturally occurring organohalogen compounds, a large fraction are alkaloids [1,3]. Most of these halogenated pyrroles, indoles, carbazoles, carbolines, tyrosines, and others have a marine origin. The present chapter surveys the occurrence, structure, and biosynthesis of these fascinating natural products. However, given their sheer number, this review focuses mainly on recent examples. 

Tunicates are the only marine invertebrates in which alkaloid biosynthesis has been extensively investigated (189). In addition to the eudistomins, described below, the tripeptide tunichromes have been investigated, by Nakanishi and coworkers at Columbia University, in the solitary tunicate Ascidia nigra (191) and shermilamine, a benzo-3,6-phenanthroline alkaloid, has been studied in Cystodytes dellechiajei, by Steffan and coworkers at the University of Munich (192). The origin of the (3-carboline ring system of the eudistomins has been studied, by Baker s group at Florida Tech, in Eudistoma olivaceum (193, 194). 

Chapter 4 by Bill J. Baker of the Florida Institute of Technology reviews "p-Carboline and Isoquinolinc Alkaloids from Marine Organisms". p-Carbolinc and isoquinoline alkaloids are some of the pharmacologically most significant marine natural products. This chapter treats the isolation, structure elucidation, synthesis, biosynthesis, and pharmacological activity of these alkaloids. 

The tunicates have been the focus of many investigations due to the biomedical potential of such metabolites as the didemnins, [118] ecteinascidins, [119 - 123] and the eudistomins [124], While the biosynthesis of the didemnins has not been investigated, the metabolic origin of the latter two families of compounds has been examined. The eudistomins are (3-carboline alkaloids produced by the tunicate Eudistoma... 

Also, a large number of indole alkaloids are formed by Mannich reactions involving tryptophan or its decarboxylation product tryptamine with various aldehydes. Both the a- and p-position of the indole nucleus are electronegative, and a Mannich reaction with tryptamine can yield a p-carboline derivative or a 3,3-spiroindolenine [30]. A further example is provided by the tropinone biosynthesis (Figure 1.29) [31 ]. 

Figure 1.29 Examples of Mannich reactions, (a) Biosynthesis of alkaloids bearing the 1,2,3,4-tetrahydroisoqumoline ring, (h) biosynthesis of indole alkaloids (P-carboline, 3,3-spiroindolenine), and (c) tropinone biosynthesis.

R.B. Herbert,. Mann,The biosynthesis of the P-carboline alkaloids, harman and elea-gnine,. Chem. Soc. Perkin Trans. 1 (1982) 1523—1525. 

Commercial Production of Ergot Alkaloids Harmane or p-Carboline Alkaloids Biosynthesis... 

P. viridis grows naturally in Amazonian tropical forests in Central and South America, and the leaves are used as one of the main components in the preparation of the hallucinogenic drink ayahuasca. This plant is a rich source of the psychedelic indole-alkaloid DMT [94] in the mixture that also contains jS-carboline alkaloids provided by Banisteriopsis caapi (Malpighiaceae), mainly harmine, harmaline, and tetrahydroharmine, that besides psychoactive properties, act as reversible MAOIs. MAO acts as a detoxifying enzyme [105], and when inhibited by MAOIs, DMT inactivation is prevented in the gut [106] enabling it to reach the CNS site of action, affording significant psychotropic effect. DMT biosynthesis is relatively simple and is summarized in Scheme 5.2. 

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