Corynantheal

The data given in the table for corynanthine are due to Foumeau and Fiore. Raymond-Hamet later found that corynanthine on alkaline hydrolysis gave a dextrorotatory acid, which Scholz confirmed and identified its methyl ester as yohimbine and suggested that corynanthine is a stereoisomeride of yohimbine. Fourneau and Benoit have confirmed that corynanthine on acid hydrolysis gives 1-corynanthic acid (m.p. 284°, [a]i) — 85-9° pyridine), but on alkaline hydrolysis, even in the cold, some racemisation occurs and the resulting acid is of low lasvo-rotation. They also point out that both yohimbine and corynanthine yield yohimbone on dehydrogenation cf., p. 504) and are probably stereoiso-merides. 

Yohimbine (36) is a well-known and reasonably available alkaloid from Corynanthe yohimbe, inter alia. For this reason, and partly because of its intrinsic pharmacological activity (including reputed aphrodisiac activity), chemists have frequently studied its properties. Oppenauer oxidation is usually attended by saponification and decarboxylation in this series, and yohimbone (37) is the product. Wolf-Kischner reduction to yohimbane (38), followed by sodium hydride mediated alkylation, leads to the analgesic agent, mimbane (39). °... 

Hirsutine (2-795), which belongs to the corynanthe subgroup of the indole alkaloids, was isolated from the plant Uncaria rhynchophylla MIQ and used for the preparation of the old Chinese folk medicine Kampo [397]. It is of pharmacological interest as it shows a strong inhibitory effect on the influenza A virus (subtype H3N2) with an EC50 = 0.40-0.57 pg ml. which is about 11- to 20-fold higher than that of the clinically used ribavirin [398]. 

B. CORYNANTHE ALKALOIDS 1. Antirhine and Antirhine jVb-Metho Salts... 

Dihydrocorynantheol (21), first isolated from Aspidosperma marcgravianum (147), is the simplest corynanthe alkaloid. The members of this type of alkaloid have three stereo centers in the D ring of the indolo[2,3-a]quinolizine skeleton. This substitution pattern allows four possible relative arrangements for the C-3, C-15, and C-20 stereo centers, the names of which are normal, pseudo, alio, and epiallo, respectively. 

Direct hydrogenation of key intermediate 248 over the Adams catalyst and subsequent lithium aluminum hydride reduction yielded the two stereoisomeric alcohols 256 and 257, which were separately transformed to ( )-corynantheal (258) and ( )-3-epicorynantheal (259), respectively, by Moffatt oxidation, followed by Wittig reaction with methyltriphenylphosphonium bromide and, finally, by demasking the aldehyde function (151, 152). 

From lactams 266 and 267 the 18,19-didehydro alkaloid corynantheal (258) and its stereosiomers with pseudo and epiallo configurations have also been prepared in racemic form (154). 

The natural antipode of corynantheine (35, 155, 20/ ) has elegantly been prepared by Autrey and Scullard (168), starting from yohimbone (305), synthesized and resolved previously by Swan (169). Yohimbone (305) was converted to 18-formylyohimbone (306) and then through 307 to oxime 308. On reaction with thionyl chloride, 308 underwent a Beckmann fragmentation to the trans-substituted indolo[2,3-a]quinolizine 310, which after desulfurization and esterification resulted in the levorotatory methyl corynantheate (304). This product... 

An interesting transformation was discovered by Sakai and Shinma (181) during the chemical investigation of corynanthe alkaloid (V-oxides. Polonovski reaction and sodium cyanoborohydride reduction of hirsuteine A-oxide (331) gave corynantheine (52) and 3-isocorynantheidine (65), the latter likely formed by reduction of the conjugated iminium intermediate 334. 

A series of publications appeared regarding the transformation of corynanthe-type alkaloids to yohimbane derivatives (285-287). The saponification of cory-nantheine (52) in methanol yielded a complex mixture of corynantheic acid (588), two C-16-epimer acetal acids (589), and demethoxycarbonylcory-nantheine (590). All four compounds upon hydrolysis in acid resulted in cory-... 

Almost nothing is known about the biosynthetic pathway between a Corynanthe intermediate and the first Aspidosperma alkaloid tabersonine (38) and, indeed, the first Iboga alkaloid catharanthine (4). Thus, the focus of further work has been the intermediates involved in the pathway... 

Yohimbine Yohimbine is methyl ether ( )-2a-hydroxyyohimban-la-carboxylic acid (12.2.16). It is isolated from the plants Corynanthe johimbe and Rauwolfia serpentina [60,61], It is also synthesized [62-66],... 

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 indole nucleus can change during the synthesizing reaction into quinoline nucleus (Figure 32). Moreover L-tryptophan, the precursor, provides both /3-carboline and pyrroloindole nuclei. Iboga, Corynanthe and Aspidosperma nuclei also originate from L-tryptophan (Figure 32). Alkaloids with nuclei derived from this amino acid tend to be very active compounds with a relatively widespread provenance in nature (Table 10). 

Three types of nucleus occur here the corynanthe, iboga and aspidosperma. 

Aspidosperma alkaloids These alkaloids have an aspidosperma-type nucleus. The a and are the same as in corynanthe type. Catharantine is the P4 from cathenamine (Figure 68). 

This group of alkaloids has two structurally different a. The a of alkaloids found in the genus Cinchona (Ruhiaceae), such as quinine, quinidine, cinchonidine and cinchonine, is L-tryptophan. The j8 is tryptamine and the

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Staerk, D., Lemmich, E., Christensen, J., Kharazmi, A., Olsen, C. E. and Jaroszewski, J. W. 2000. Leishmanicidal, antiplasmodial and cytotoxic activity of indole alkaloids from Corynanthe pachyceras. Planta Medica, 66 531-536. 

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