Alkaloids 3-carbolines

Manzamine alkaloids ((3-carboline derivatives from sponges), syntheses and synthetic approaches 98T6201. 

Biogenesis of manzamine alkaloids ((3-carboline marine alkaloids) 97H(46)765, 97YGK1114. 

L-tyrosine Tyrosine-derived alkaloids Indole alkaloids Quinoline alkaloids /3-carboline alkaloids Pyrroloindole alkaloids Ergot alkaloids Iboga alkaloids Corynanthe alkaloids Aspidosperma alkaloids Protoalkaloids Terpenoid indole alkaloids True alkaloids... 

The roasted root contains a steam-distillable fraction (aroma), which is composed of pyra-zines, benzothiazoles, aldehydes, aromatic hydrocarbons, furans, phenols, organic acids, and others, totaling 3 3 identifiedcompounds, among which acetophenone is a characteristic component of roasted chicory not previously reported as a component of aroma of any heated food products such as coffee. Other constituents of the roasted root include 2-acetylpyrrole, furfural, phenylacetaldehyde, phenylacetic acid, and vanillin. Small amounts oftwo indole alkaloids ((3-carbolines), barman and norharman, have also been isolated from the roasted root. ... 

Conducted in an intramolecular sense, both Mannich and Vilsmeier reactions have been much used for the construction of tetrahydro-/3-carbolines (dihydro-/ -carbolines), such as are found in many indole alkaloids (/ -carboline is the widely-used, trivial name for the pyrido[3,4-Z>]indole). 

Barger el al. took the view that the alkaloid contains two tryptamine residues, one represented in the degradation products by -methyltrypt-amine, and the other by methyl-3-carboline, and on this basis proposed formula (II). Manske and Marion, on the contrary, regard 2V-methyl-tryptamine and 3-carboline as originating from the same moiety of the molecule, the other half being represented by 4-methylquinoline, and on this conception based formula (III). 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

The Bischler-Napieralski reaction involves the cyclization of phenethyl amides 1 in the presence of dehydrating agents such as P2O5 or POCI3 to afford 3,4-dihydroisoquinoline products 2. This reaction is one of the most commonly employed and versatile methods for the synthesis of the isoquinoline ring system, which is found in a large number of alkaloid natural products. The Bischler-Napieralski reaction is also frequently used for the conversion of N-acyl tryptamine derivatives 3 into p-carbolines 4 (eq 2). 

This reaction is also a key method for the formation of tetrahydro-P-carbolines 5 from indole bases 4 and aldehydes, ketones, or 1,2-di carbonyl compounds 2. These reactions are similarly acid-catalyzed or thermally-induced and have been utilized in the synthesis of numerous indole alkaloids. 

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

This review is an attempt to collect under one heading and to present in a systematic manner the large body of work which deals with the chemistry of the carboline ring systems. Some three hundred papers in this field have been published during the last decade, more than twice as many as appeared during the preceding fifty years. The renewed interest in the chemistry of the carbolines is due in no small measure to the discovery of serotonin and to the recent developments in the chemistry and pharmacology of the Rauwolfia and related alkaloids. 

It is not proposed to discuss these topics, which have been adequately reviewed elsewhere, but to focus attention on general aspects of carboline chemistry, including relevant findings which emerged incidentally in the course of degradative and synthetic work in the field of indole alkaloid chemistry. The only published review on the carbolines emphasizes aspects of the work carried out prior to 1950. 

The nomenclature used to describe the fused benzene-pyrrole-pyridine system of the compounds under discussion has been repeatedly modified, and the compounds have been numbered in an astonishing variety of ways since Perkin and Robinson introduced the name carboline for the ring system, which was encountered for the first time in the harmala alkaloids. In the earliest version of carboline nomenclature, the parent compound of the series, whose trivial name was norharman, was referred to as 4-carboline and numbered as in 1. Harmine (2) then became ll-methoxy-3-methyl-4-carboline. 

A variety of l,2,3,4-tetrahydro-j8-carbolines have been prepared from 3-piperidone phenylhydrazone derivatives. Used initially to obtain pentacyclic derivatives (35) related to the yohimbe alkaloids, this route was later extended to the synthesis of tetracyclic compounds (36). l-Methyl-5,6,7,8-tetrahydro-j8-carboline (37) was prepared in low yield by heating cyclohexanone 2-methyl-3-pyridylhydrazone with zinc chloride, a synthesis probably based on the similar preparation of the tetracyclic compound 38 starting from the corresponding quinolylhydrazine. Abramovitch and Adams extended this approach to the cyclization of cyclohexanone 3-pyri-dylhydrazone (39) itself. The main product was 6,7,8,9-tetrahydro-8-carboline (40), a smaller amount of the j8-isomer (41) also being obtained. This provides a convenient and readily reproducible route to the otherwise difficultly accessible 8-carboline ring system. The favored attack at carbon-2 over carbon-4 of the pyridine nucleus... 

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. 

In the course of structural investigations of a number of jS-carboline alkaloids, reactions leading to ring cleavage have been encountered. Oxidation of harmine (271) and of harmaline... 

Cleavage of the hetero ring in a number of extended tetrahydro-j8-carboline systems was observed in the course of structural elucidation of tetrahydro-jS-carboline alkaloids. A few examples only will be given. The indole derivative 287 was isolated as one of the products of the selenium dehydrogenation of yohimbine (358 R = and... 

The alkaloid rutaecarpine (111) was synthesized from l-oxo-1,2,3,4-tetrahydro-)3-carboline (183 R = H) by condensation with methyl anthranilate in the presence of phosphorous chloride or by heating... 

Carboline and isoquinoline alkaloids from marine organisms 96MI5. 

The inverse electron demand Diels-Alder reaction has also been used to provide expedient access to unnatural 6-carboline alkaloids from 1,2,4-triazines, prepared by microwave-assisted MCR [92]. One-pot reaction of an acyl hydrazide-tethered indole 73, 1,2-diketone and ammonium acetate in acetic acid provided triazines 74 (see Sect. 3.2, Scheme 22), bearing an electron-rich dienophilic indole moiety (Scheme 31). By carrying out the... 

Carboline alkaloids Hedy Otis capitellata SiOj Cx + CHCI3 + EtjNH - Identification 20... 

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