Tetrahydro-3-carbolines, oxidation

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... 

Ajmalicine66", and several synthetic tetrahydro- -carbolines,6 6 have been converted in high yields, by aerial oxidation in the presence of strong base, into compounds having portions of the skeleton of camptothecin. Thus ajmalicine660... 

Oxidative reactions of tetrahydro- -carbolines and results of electron impact... 

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. 

Similar oxidative reactions have been studied more thoroughly in the pentacyclic series of tetrahydro-j8-carbolines, and general methods are available. 

Those epimers of 1,2,3,4-tetrahydro-j8-carbolines of general structure 139, in which the hydrogen on carbon-1 of the carboline moiety is axial, are converted into the corresponding 3,4-dihydro- -carbolinium salts (141) by mercuric acetate oxidation. Sodium dichromate... 

Non-oxidative conversion of a tetrahydro-)8-carboline into a 3,4-dihydro derivative has also been described. Dehydration of 1-hydroxymethyl-1,2,3,4-tetrahydro-j8-carboline (146) yielded 1-methyl-3,4-dihydro-j8-carboline (135). Harmaline and l-methyl-3,4-dihydro-j8-carboline-3-carboxylic acid were obtained in an analogous manner. ... 

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... 

A series of oxidative rearrangements of tetrahydro-j8-carbolines may be rationalized on the basis of a general reaction of 2,3-disub-stituted indoles which was recently recognized by Taylor. Attack at the 4a-position of the tetrahydrocarboline (341) by an electrophile yields the indolenine derivative 342, which is in equilibrium with the isomeric species 342a. Compounds of structure 342 and 342a can undergo a variety of reactions leading to different products. 

The oxidation of tetrahydro-j8-carboline to dihydro-jS-carbolinium salts (341-> 342 342a->343) by -butyl hypochlorite (X = Cl), dichromate, or mercuric acetate (cf. Section III,C, 2,b), followed, by treatment with acid, and to j8-carbolinium salts (341 ->344) by lead tetraacetate [X = Pb(OAc)3] (cf. Section III, E, 2, a, ii) in acid solution... 

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... 

Support for this suggestion comes from many quarters. Reduction of the jS-carboline anhydro-bases with sodium and alcohol or with tin and hydrochloric acid gives the 1,2,3,4-tetrahydro derivatives, as does catalytic reduction over platinum oxide in an alkaline medium. On the other hand, catalytic reduction with platinum oxide in acetic acid results in the formation of the 5,6,7,8-tetrahydro-j3-carbolinium derivatives (see Section III,A,2,a). It should be noted, however, that reduction of pyrido[l,2-6]indazole, in which the dipolar structure 211 is the main contributor to the resonance hybrid, could not be effected with hydrogen in the presence of Adams catalyst. 

These authors formulated the major steps in the biogenesis of the harmala bases as a condensation of a tryptamine derivative (460) with acetaldehyde to yield a l,2,3,4-tetrahydro-)3-carboline (461), which on oxidation in two stages would give harmaline (462 R = OCH3) and then harmine (463 R = OCH3). 

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... 

Han, QP and Dryhurst, G (1996) Influence of glutathione on the oxidation of l-methyl-6-hydroxy-l,2,3,4-tetrahydro-beta-carboline chemistry of potential relevance to the addictive and neurodegenerative consequences of ethanol use. J. Med. Chem. 39 1494-1508. 

Tietze adopted a somewhat more indirect route to enantiopure tetrahydro-p-carbolines 166. This approach begins with P-S reaction of tryptamine with aldehydes or a-keto acids to yield the carbolines 163, which upon oxidation to the corresponding imines 164 subsequently undergo enantioselective hydrogenation with the catalyst 165 in a 5 2 formic acid/triethylamine mixture in acetonitrile <00EJO2247>. 

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