Carboline blue

The intense blue color which is obtained when tryptophan, in the presence of an aldehyde, is treated with concentrated sulfuric acid containing an oxidizing agent (Adamkiewicz-Hopkins-Cole reaction) was beheved to involve formation of a tetrahydro-j8-carboline intermediate, since most l,2,3,4-tetrahydro-j8-carbohne 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. 

Leonard and Elderfield have also carried out degradation experiments with alstonine and its tetrahydride. On fusion with potassium hydroxide at 300-350° in nitrogen, alstonine furnishes barman (p. 490) and indefinite basic and acidic fractions. Tetrahydroalstonine on like treatment produces barman, worharman, and three unidentified bases, each of which fluoresces blue in alcoholic hydrochloric acid Base A, C4,H4gN2, m.p. 171-5 to 172-5°, forms a picrate, m.p. > 267° is probably a substituted -carboline. Base B, or 18 3, gives apicrate, m.p. 261° (dec.). Base C,... 

For the synthesis of the natural blue pigment trichotomine dimethyl ester, L-Trp-OMe was used as a starting material. The first step of this synthesis was conversion into methyl l-methyl-3,4-dihydro-/8-carboline-3-carboxylate with acetyl chloride in TFA (85JOC3322). An improved method starts from the corresponding thioamides via thioiminium salts which cyclize spontaneously in refluxing solvent (82CPB4226). A-Formyl-tryptophan also cyclized readily with no side reactions (68CJC3404). 

Scheme 40 Synthesis of the tetrahydro-/ -carboline scaffold 221. Two representative diastereo-mers of 221A are drawn in blue and cyan...

Bauerines A-C (50-52) are chlorinated p-carbolines from the blue-green alga Dichothrix baueriana that show activity against herpes simplex virus type 1 [49]. 

A 6-cyano-5-methoxy-12-methylindolo[2,3-a]carbazole and 6-cyano-5-methoxyindolo[3-a]carbazole were isolated from the blue-green alga Nostoc sphaericum [95]. These compounds are active against HSV-1. Larsen ct al. [96] isolated three new chlorine-containing P-carbolines, bauerines A-C, from the blue-green alga Dichothrix baueriana. These alkaloids show activity against HSV-2. 

Fig. 9A Harmalae semen. The carbolin derivatives harmalol (Tl), harmaline (T2) and harmine (T4) are found as bright blue fluorescent zones in solvent A in the R, range 0.1-0.75. The Harmalae semen sample 1 shows as major alkaloids harmalol and harmaline in the low Rf range 0.05-0.25 and harmine in the upper Rf range 0.75.

Larsen, L.K. Moore, R.E. Patterson, G.M.L. b-Carbolines from the Blue-Green Alga Dichothrix baueriana. J. Nat. Prod. 1994,57, 419-421. 

Harmane (2-methyl-p-carboline, l-methyl-9Ff-pyrido[3,4- ]indole, Aribine) [486-84-0] M 182.2, m 235-238 , 237-238 , pKi 7.37 (basic. Pry N), pK214.7 (acidic, NH). Crystallise it from heptane/cyclohexane. It is insoluble in H2O, but soluble in dilute HCl or H2SO4. Solutions show a blue fluorescence. Its UV (MeOH) has Xmax nm (log s) at 234 (4.57), 287 (4.21) and 347 (3.66). The hydrochloride forms needles from EtOH/dil HCl which sublimes at m 120-130 . It is an imidazoUne binding site agonist. [Wolfbeis ATonatsA CAew 113 509 1982, Beilstein 23/12 237.]... 

A few indole-based compounds are active against viruses (Scheme 24). The non-nucleoside reverse transcriptase inhibitor delaviridine (163) is used in antiretroviral therapy [150]. The blue-green alga Dichothrix baueriana has yielded bauerine B (164), a dichloro p-carboline active againstherpes simplex virus type 1 [169]. Seeds of the plant Solarium indicum have yielded the new coumarinolignoid indicumine B (165), which possesses anti-hepatitis B... 

Several p-carboline alkaloids were synthesized via Fischer indole methodology. For example, the blue-green alga Dichothrix baueriana alkaloids bauerines A, B, and C were synthesized by two groups via a Japp-Klingemann approach (Scheme 43, equations 1 and 2) [282,283]. Only the routes to bauerine C (140) are shown. Bauerines A and B were prepared in poor yields by reduction of the Fischer indole lactam product and DDQ oxidation of the tetrahydro-p-carbolines. Islam s synthesis [283] of bauerine C is essentially identical to that of Bracher [282], and in roughly comparable yields. A Fischer indolization was... 

The bitter taste and blue fluorescence of the flesh of the toadstool Cortinarius infractus are due to P-carboline derivatives 613). From the methanolic extract of freeze dried fruit bodies have been isolated infractin (527) showing bright blue fluorescence under UV light, 6-hy-droxyinfractin (528) which fluoresces green-yellow, and a bitter principle, infractopicrin (529). The yellow pigment (528) [UV/vis. (methanol) max(log 8) = 214 (4.36), 231 (4.53), 246 (4.37), 258 (4.24), 290 (sh., 4.14), 296 (4.33), 360 (3.72)] has been synthesised according to the reactions depicted in Scheme 84 567). 

Tryptamine, an equimolar amount of methylene blue as sensitizer, and acetic acid irradiated under Ng at ca. 20° with four 300 w. tungsten lamp 1-methyl-y -carboline. Y 93%. F. e. s. G. Cauzzo and G. Jori, J. Org. Chem. 37, 1429 (1972). 

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... 

In a third example case, p-carbolines are inhibitors of monoamine oxidases (MAO-A and MAO-B) and can be found in foods, hallucinogenic plants or certain plant dmgs. The referred article described a fast analysis method for p-carbolines based on the inhibition of MAO [79]. The MAO-A is inhibited by all three tested P-carbolines (harmane, norharmane and harmaline), while MAO-B is inhibited only by norharmane. The presence of norharmane in mixtures of p-carbolines can be identified based on the difference between the cumulative inhibition of MAO-A by all p-carbolines and MAO-B inhibition. The enzymes were immobilized on screen-printed electrodes modified with a stabilized film of Pmssian blue that contain also copper. Benzylamine was used as substrate for the enzymatic reaction and the hydrogen peroxide formed was measured amperometrically at —50 mV. The developed biosensors were used for food analysis. The detection limits obtained were 5.0 pM for harmane and 2.5 pM for both harmaline and norharmane. 

Irradiation of tryptophan with visible light in acetic or formic acid solution in the presence of methylene blue gives good conversion to a P-carboline (215). The reaction probably proceeds via OH abstraction from the solvent molecule by photoexcited methylene blue, with formation of an acyl RC = 0 radical, which attacks the 2-position of the indole substrate. The 2-acyl derivative cyclizes to the dihydro-p-carboline (82) which is aromatized by methylene blue photosensitized dehydrogenation to (83). p-Carbolines variously substituted in the 1- or 3-position have been obtained by an appropriate choice of the solvent and indole side chain. 

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