Carbolines reduction

R" = CH20H). The use of sodium borohydride in place of lithium aluminum hydride did not lead to ring closure but to 3-[j8-(A-l,2,3,4-tetrahydroisoquinolyl)ethyl]indole derivatives (53). Reductive cyclization by means of lithium aluminum hydride of the j8-(3-indolyl)ethyl-l-isoquinoline (52) to the pentacyclic tetrahydro-j8-carboline 49 (R = R = R" = H) has been reported. Strong acid alone sufficed to convert 52 into 54, the 0x0 derivative of 49. ... 

Tetrahydrocarboline derivatives have recently been synthesized from 2-o-nitroarylated cyclohexanone derivatives. Thus, reductive cyclization of 3-(2,4-dinitrophenyl)-l-methyl-4-piperidone (68) (prepared by the reaction of 2,4-dinitrochlorobenzene with l-methyl-4-A-pyrrolidmo-3-piperideine) gave 7-amino-2-methyl-l,2,3,4-tetrahydro-y-carboline (69). Neither catalytic nor chemical reduction of the... 

Homoesermetol (1,4a,9-trimethyl-6-methoxy-1,2,3,4,4a, 9a-hexa-hydro-a-carboline (89 R = CH3, R = OCH3) may be prepared in a manner analogous to that used for the preparation of eseroline. Thus, when the 3-y-oxindolylpropylamine 88 (R = CH3, R = OCH3) is reduced with sodium in butanol, homoesermetol is obtained. Reductive cycbzation of 88 (R = R = H) with lithium aluminum hydride has recently been reported. 

The reduction of 2-methyl-1,2,3,4-tetrahydro-y-carboline (92) with zinc and hydrochloric acid in the presence of mercuric chloride gives the indolenine derivative, 2-methyl-l,2,3,4,4a,9b-hexahydro-y-carbo-line (93). A related compound, 4,9b-diethyl-2-methyl-l,2,3,4,4a,9b-hexahydro-y-carboline (96), was obtained by catalytic hydrogenation of 95, which was prepared by Fischer ring closure of the phenyl-hydrazone 94. The stereochemistry of the B/C ring junction in these... 

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,... 

The oxidative and reductive interconversions of different oxidation states of the carboline ring system are systematically discussed in Section III. 

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. 

Another total synthesis used the rich chemistry of iminophosphoranes (95AHC159). The /3-(3-indolyl)vinyl iminophosphorane 354 underwent an aza-Wittig/electrocyclic ring closure reaction to give the carboline 355 which was hydrolyzed with lithium hydroxide (Scheme 106). A selective reduction, deprotection, decarboxylation and diazotation followed by ring closure gave Fascaplysine (353) (94TL8851). 

In summary, based on the results of relatively limited studies, the dihydro beta-carboline, harmaline (80), is more active than either its fully unsaturated derivative harmine (79) or its reduced derivative tetrahydroharmine (81). The positional isomer of harmine, 6-methoxyharmalan (85), is slightly more potent than harmaline. Reduction to the tetrahydro derivative 86 reduces potency. Although thorough dose-effect studies have not yet been performed, none of the beta-carboline derivatives has been found to be significantly more potent than DMT (37). 

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