Indole derivatives alkaloids

Hydroxyrutaecarpine. In the first report of a series involving various indole-derived alkaloids, Clark and co-workers reported the structure of the indolopyrido-quinazoline alkaloid 3-hydroxyrutaecarpine (16) isolated from Leptothyrsa sprucei. 

An indole-derived alkaloid Synonyms (16a, 17a )-17-hydroxyyohimban-16-carboxylic acid methyl ester corynine aphrodine quebrachine... 

To demonstrate the power of these cascade sequences this methodology was successfully applied to total syntheses of several indole-derived alkaloids, for example, minfiensine [113]. By implementation of organocatalyzed cascade reactions the MacMillan group was able to dramatically reduce the number of reaction steps in total syntheses of strychnine, aspidospermidine, and kopsinine [114]. 

Three new papers bearing on the structure of strychnine have become available too late for inclusion in this summary of recent work. Woodward, Brehm and Nelson have compared the ultra-violet absorption spectra of strychnine and Leuchs s strychnone (p.. 559) and used the results for a discussion of the relationship of the two alkaloids. Prelog and Kathriner have investigated the oxidation of strychnine, i/t-strychnine and brucine by permanganate in weakly acid solution and Bailey and Robinson from a study of the brucones have confirmed the conclusion of Woodward et al. that Leuchs s strychnone is a true indole derivative. Mention must also be made of a paper by Clemo and King on new reduction products of strychnine, of which a preliminary account has been published with a summary of the ensuing discussion. 

Rauwolscine gives colour reactions like those of yohimbine and the absorption curves of the hydrochlorides of the two alkaloids are very similar. Heated to 300°/5 mm. rauwolscinic acid forms barman (p. 490) and 3-ethylindole and on fusion with potassium hydroxide decomposes into indole-2-carboxylic acid, isophthalic acid, barman and an unidentified indole derivative. Rauwolscine itself on distillation with zinc dust produces barman, 2-methylindole (scatole) and tsoquinoline. It is suggested that the alkaloid has the skeletal strueture suggested by Seholz (formula XIV, p. 508) for yohimbine, the positions of the hydroxyl and earbomethoxy grouf s being still imdetermined. 

The alkaloid iboquine, a piperidinoquinoline, was derived in an analogous manner by air-oxidation of ibogaine, an indole derivative. 

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... 

During studies on the acid-induced formation of the alkaloid yuehchukene and related structures from pienylindoles, it was discovered that treatment of indole 173 with p-toluenesulfonic acid and silica gel leads to the formation of indolo-[3,2-b]carbazole 174 and the indole derivative 175 (Scheme 21). Similarly, the disubstituted product 176 could be isolated after TFA treatment of the substrate 177. Detailed mechanistic explanations have also been provided in this work (96T9455). 

Waldmann used (R) and (5>aminoacid methyl esters and chiral amines as chiral auxiliaries in analogous aza-Diels-Alder reactions with cyclodienes.111 The diastereoselectivity of these reactions ranged from moderate to excellent and the open-chain dienes reacted similarly. Recently, the aza-Diels-Alder reaction was used by Waldmann in the asymmetric synthesis of highly functionalized tetracyclic indole derivatives (Eq. 12.45), which is useful for the synthesis of yohimbine- and reserpine-type alkaloids.112... 

Scheme 4.6 The common core structure of many indole monoterpene alkaloids might be accessed through a tetracyclic Zincke aldehyde-derived building block...

We became particularly interested in strychnine when we noticed that the tetracycle 21 (Scheme 4.6), which might be readily available by an intramolecular Diels-Alder cycloaddition of a tryptamine-derived aminodiene, contains much of the complexity of this popular alkaloid target. In fact, this tetracycle is common to many indole monoterpene alkaloids including members of the Strychnos, Aspidosperma, and... 

Table 4 illustrates the use of the CAR technique to develop CL kinetic-based determinations for various analytes in different fields. As can be seen, the dynamic range, limit of detection, precision, and throughput (—80-100 samples/ h) are all quite good. All determinations are based on the use of the TCPO/ hydrogen peroxide system by exception, that for p-carboline alkaloids uses TCPO and DNPO. A comparison of the analytical figures of merit for these alkaloids reveals that DNPO results in better sensitivity and lower detection limits. However, it also leads to poorer precision as a result of its extremely fast reactions with the analytes. Finally, psychotropic indole derivatives with a chemical structure derived from tryptamines have also been determined, at very low concentrations, by CAR-CLS albeit following derivatization with dansyl chloride. 

Indole derivatives are widespread natural compounds, and mass spectrometry of indole derivates, [225,226] especially of indole alkaloids, has been a topic of interest ever since. [227-229]... 

Moreover, polycyclic indole alkaloid-type molecules 225 with a ketopiperazine were prepared by Wang et al. using Ugi-Pictet-Spengler process [68]. Ketocar-boxylic acids 227 were used as bifunctional substrates in Ugi reaction to yield lactams of varying ring sizes (Scheme 41). A diastereomer of hexacyclic indole derivative was crystallized and yielded X-ray diffraction suitable crystal to assign the stereochemistry. 

Syntheses of /3-carbolines and /3-carboline derived alkaloid 17a-epoxyapovi-caminate from indole oximes were described. For example, oxime 306 in o-dichlorobenzene at 190 °C cyclized to carboline 307 in 81% yield (equation 132). 

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 best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

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