J8 Carboline derivative

Anhydro-bases derived from quaternary )S-carbolinium salts are reduced to p /r-A-substituted-l,2,3,4-tetrahydro-j8-carboline derivatives on hydrogenation over Adams catalyst in methanol solution made alkaline to ensure the presence of anhydro-base. ... 

A large number of compounds containing an extended 3,4-dihydro-/5-carbolinium system (82) have been converted similarly into the corresponding tetrahydro-j8-carboline derivatives (83a and 83b). In many cases the reaction is stereospecific and one or the other of the epimers 83a and 83b has been isolated as the sole or major product. Sodium and ethanoH tin and hydrochloric acid zinc and... 

Polycyclic derivatives have been prepared by straightforward amide formation. The tetracyclic amide 166 was obtained by reductive cyclization of 3-o-nitrophenylindole-2-carboxylic acid (165).22 When l-(2 -ethoxycarbonylskatyl)isoquinoline (167) was heated the pentacyclic j8-carboline derivative 168 was formed. If,... 

It is interesting to note that whereas 7-methoxy-l-methyl-l,2,3,4-tetrahydro-jS-carboline condenses with diazobenzenesulfonic acid to give an azo compound (presumably the 6-arylazo derivative) and 7-methoxy-l-methyl-3,4-dihydro-j8-carbohne gives a bisazo compound, none of the fully aromatic j8-carboline derivatives studied by Perkin and Robinson underwent azo-coupling. 

Reaction of j8-carboline derivatives with hydrogen peroxide or perbenzoic acid and of S-carboline with peracetic acid yields the corresponding yr-A-oxide (e.g. 280). 

It is possible that the 7-methoxy group is necessary to render the benzene ring of these j8-carboline derivatives susceptible to oxidative attack. However, a y-carboline derivative (285) has been reported to undergo an analogous oxidation and decarboxylation. ... 

The reactivity of the 1-methyl group and of corresponding positions (i.e., a-carbon atoms) in other l-alkyl-j8-carbolines, analogous to that in a-picoline, quinaldine, and isoquinaldine, is due to the acidity of this center. Deprotonation yields a resonance-stabilized anion (288) which reacts readily with electrophilic reagents. Metallation with phenyl-lithium of the 1-methyl group of a l-methyl-j8-carboline derivative in which the indole nitrogen is protected, first described by Woodward... 

Only in one case was the structure of the adduct rigorously established, but it would appear most likely that these adducts are 1-cyano- or 1 -hydroxylamino-1,2,3,4-tetrahydro-j8-carboline derivatives (308). 

Acetylation of a 3,4-dihydro-j8-carboline derivative has been reported. O. Fischer described an A-acetylharmaline which was formulated as 310 since on controlled permanganate oxidation it yielded a neutral product (311), which on hydrolysis gave 7-methoxy-l-oxo-l,2,3,4-tetrahydro-j8-carboline (313) the constitution of 313... 

An analogous acylation reaction has been described in another 3,4-dihydro-j8-carboline derivative. The amide 315, on Bischler-Napieralski ring closure with phosphorus oxychloride, yields an... 

Acylation of l,2,3,4-tetrahydro-j8-carboline derivatives takes place preferentially at the pyr-N. Thus l,2,3,4-tetrahydro-j8-carboline yields a 2-formyl and a 2-acetyl derivative, which give 2-methyl- ... 

A number of intramolecular rearrangements of 1,2,3,4-tetrahydro-j8-carboline derivatives have been reported. Some of these lead into other naturally occurring heterocyclic ring systems and are therefore of particular interest. 

The acid-catalyzed conversion of the l,2,3,4-tetrahydro-j8-carboline derivative 337 (R = CHg) into the strychnine-type ring system 338 has been attributed to an equilibrium involving the protonated Schiff s base 339 of tryptamine (i.e., the intermediate in the Pictet-Spengler type synthesis of tetrahydro-j8-carbolines, cf. Section III, A, 1, a), and the a- (337) and the j8-condensation products (340). 

The Hofmann and Emde degradation of tetrahydro-j8-carboline derivatives has been reported in a number of instances, but only in one... 

The benzindolopyrrocoline system (413) was obtained by oxidative cyclization of the l-benzyl-l,2,3,4-tetrahydro-j8-carboline derivative (337 R = H or CHg) using either ferricyanide or silver oxide, a reaction analogous to that described by Robinson and by Schopf... 

Carboline derivatives in various oxidation states have been isolated from a number of natural sources as artifacts. )3-Carboline has been obtained from charred insects, j8-carboline and l-methyl-)3-carboline have been found in cigarette smoke,and the formation of tetrahydro-j8-carboline derivatives has been shown to be responsible for the destruction of tryptophan in acid hydrolyzates of proteins. The golden-yeUow fluorescence observed when enterochromaffin cells are flxed in formaldehyde has been related to their content of... 

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

VIII) may be briefly summarized as follows. Villalstonine is a dimeric, diacidic base, which contains one methoxycarbonyl group, two methyl-imino groups, and an ethylidene group. Its UV spectrum is consistent with the presence of indole and dihydroindole chromophores containing no substituents in the benzene rings. Alkali fusion yields 2-methylindole, indole 2-carboxylic acid, and a /3-carboline derivative selenium dehydrogenation also affords a j8-carboline derivative, so far unidentified. Acid hydrolysis of villalstonine yields pleiocarpamine (XV), one of the alkaloids of Pleiocarpa mutica Benth. 

First described by Kaljuste and Unden [34], the reaction of polymer-bound tryptophan with a variety of aldehydes and ketones under Pictet-Spengler conditions [35] has also been reported by Mayer et al. [36]. The j8-carboline derivatives 5 exhibited significant bioactivity. Following incorporation of 9-fluorenylmethoxycarbonyl (Fmoc)-tryptophan and deprotection, the condensation with an aldehyde or ketone under acidic conditions provided the /3-carbolines in high yield and purity. The same strategy has been published... 

The l,2,3,4-tetrahydro-j8-carboline pharmacophore is an important structural element in several tryptophan-derived natural product alkaloids. A soluble polymer supported synthesis of l,2,3,4-tetrahydro-j8-carboline derivatives was reported by Wu and Sung. The one-pot condensation of Fmoc-protected tryptophan anchored to MeO-PEG-OH via an ester linkage has been performed with a variety of aldehydes and ketones under the action of microwave irradiation to provide immobilized l,2,3,4-tetrahydro-yS-carboline derivatives these were liberated from the soluble matrix in good yield and high purity [123]. 

The intense blue color which is obtained when trjptophan, in the presence of an aldehyde, is treated with concentrated sulfuric acid containing an oxidizing agent (Adamkiewicz-Hopkins-Cole reaction) was believed to involve formation of a tetrahydro-j8-carboline intermediate, since most l,2,3,4-tetrahydro-j8-carboline derivatives yield a similar color with concentrated sulfuric acid containing an oxidizing agent. The two colors have now been shown to have different absorption spectra. The nature of the carboline-blue color is still obscure. 

In a recent variation of this synthesis of the tetrahydro-j8-carboline system, hexahydro derivatives (65) of the salt 55 were cyclized to fully aromatic j8-carboline derivatives (66a and 66b) on palladium dehydrogenation, presumably by way of an enamine intermediate. ... 

Finally, mention should be made of the addition of nucleophilic reagents to the 1-position of 3,4-dihydro-j8-carbolines. Cyanide has been reported to yield adducts with harmaline, 6-nitroharm-aline, and 2-methylharmalinium salt similarly, hydroxylamine forms adducts with harmaline, 3,4-dihydro-j8-carboline (307 R = H), and l phenyl-3,4-dihydro-j8-carboline (307 R = CeHg). Only in one case was the structure of the adduct rigorously established, but it would appear most likely that these adducts are 1-cyano- or l-hydroxylamino-l,2,3,4-tetrahydro-j8-carboline derivatives (308). 

Tertiary pyr-i r-alkyl-l,2,3,4-tetrahydro-j8- and -y-carboline derivatives can be quatemized at the same site to give 2,2-dialkyl-l,2,3,4-tetrahydro-j8- and -y-carbolinium salts. Tertiary tetrahydro-j8-carboline derivatives have been reported to 3deld pyr-iV -oxides. ... 

It has been suggested that the blue-green fluorescence produced when 5-hydroxy1ayptamine is treated with ninhydrin is due to the formation of j8-carboline derivatives and that a brilliant orange-red... 

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