Canthin alkaloids

Snyder has conducted similar chemistry but with the goal of generating carbon skeletons for the total synthesis of alkaloids. Using indole 84 as a dienophile, the canthine alkaloid skeleton 85 was produced. Access to aspidosperma alkaloids was obtained when 86 was transformed into 87. 

Scheme 6.269 One-pot preparation of the tetracyclic canthine alkaloid skeleton.

In the synthesis of a compound library of allosteric Akt kinase inhibitors 39, Lindsley and coworkers employed different HTS techniques (Scheme 24) [54]. A polymer-supported base and a fluorous thiol scavenger were used in the alkylation reaction of 40. F-SPE purified intermediate was then used for microwave-assisted cycloaddition of 41. Similar intermediates have been used for generation of an unnatural canthine alkaloid library 42 by performing cycloaddition reactions with an indo-tethered acyl hy-drazide [55]. 

Cytotoxic Quassinoids, Linear Triterpenes and Canthin Alkaloids from Eurycoma longifolia [38,39]... 

Eurycoma longifolia Jack (Simaroubaceae), a famous folk medicine known as "Pasak Bumi" in Southeast Asia, has been used as an antimalaria and tonic etc. The roots of E. longifolia collected in Indonesia were treated with 50% aqueous methanol, TTie extract was partitioned between water and ether, then n-butanol successively. The chromatographic purification of ether and n-butanol soluble fractions furnished canthin alkaloids (34 -36) and quassinoids (37 - 42), respectively. Their structures were coiifirmed as shown in Fig. 5 by various spect data or comparison with... 

Progress in the synthesis of canthine alkaloids and ring-truncated congeners 13JNP455. 

Tetracyclic /3-carboline alkaloids, known as canthines, have a peri-fused indolo[3,2,Tnaphthyridine structure. Over 40 members of this class of compound have been isolated, and they are of interest on account of their broad range of pharmacological effects (antimicrobial, cytotoxic, antibacterial, anticancer). 

Canthin-6-one, which is a cytotoxic alkaloid, is synthesized in six steps from harmalane (Scheme 84) <1999TL7075>. The second step is a [4+2] cycloaddition with methyl 2-(dimethylamino)acrylate under singleelectron-transfer electrolysis. 

A method was developed for preparation of the tetracyclic carboline alkaloids iso-canthine, isocanthin-6-one and l-methylisocanthin-3-one by an intramolecular hetero-Diels-Alder reaction. For example, oxime 317 in sulfolane at 285 °C afforded isocanthine 318 in 8% yield (equation 137) . 

Acetyl-3-methoxycarbonyl-/ -carboline, the alkaloid of Vestia lycioides, has been synthesized by two routes 200,6 the second involves the benzylic oxidation-dehydrogenation of l-ethyl-3-methoxycarbonyl-l,2,3,4-tetrahydro-/ -carboline by means of selenium dioxide in dioxan. A by-product in this oxidation was 1 -acetyl-/ -carboline, which occurs in Ailanthus malabarica. An extension of this reaction led to a simple two-stage synthesis of canthin-6-one (22) from Ab-benzyltryptamine and a-ketoglutaric acid (Scheme 2).206... 

The root bark of Ailanthus altissima Swingle contains the known alkaloids canthin-6-one (22), l-methoxycanthin-6-one, canthin-6-one A-oxide, and 1-acetyl-4-methoxy-/ -carboline, together with three new alkaloids, identified as 1-methoxy-canthin-6-one A-oxide, l-(2-hydroxyethyl)-4-methoxy-/ -carboline, and 1(1,2-dihydroxyethyl)-4-methoxy-/ -carboline.21... 

A synthesis of XIV was accomplished as follows (9) /J-carboline-1-carboxylic acid chloride was condensed with the magnesium ethoxy derivative of malonic ester to yield, after acid hydrolysis, 4-hydroxy-canthin-6-one (XV). This compound, with phosphorous oxychloride followed by heating in a sealed tube with potassium methyl mercaptide, gave the alkaloid XIV. If 4-hydroxycanthin-6-one is condensed with phosphorous oxychloride-phosphorous pentachloride, 4,5-dichlorocan-thin-6-one and 4-hydroxy-5-chlorocanthin-6-one are formed. 

Using this methodology, the cytotoxic alkaloid canthin-6-one LXVIIIb has been synthesized in a short sequence with good overall yield [248d]. 

In 1952, Haynes et al. (7) isolated an alkaloid from Pentaceras australis (Rutaceae) grown in Australia. This alkaloid, with the molecular formula C14H8N2O, was named canthin-6-one (1). Giesbrecht et al. (2) later isolated a new type of alkaloid, 3-methoxycanthin-2,6-one (2), from Simaba cuspidata of Brazil. Then Ohmoto and Koike (5) isolated... 

Several kinds of j8-carboline derivatives have been isolated from fungi since the first isolation of canthin-6-one alkaloids from this toadstool. 

Taylor (5) reviewed some of the canthin-6-one alkaloids such as canthin-6-one (1), 4-methylthiocanthin-6-one (6), 5-methoxycanthin-6-one... 

Thirty-five canthin-6-one alkaloids have been isolated from 36 species... 

Canthin-6-one (1) has been isolated from 25 of the 36 species of plants in Table I and from cell cultures of Ailanthus altissima (13-16). Canthin-6-one is one of the most widely distributed alkaloids in plants. It has been reported (77) that 1 is contained in 9 of 33 species in the genus Rhododendron of the family Ericaceae of China. Readers are referred to Volume 8 (p. 249) of this treatise for its structure (5). 

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