Piperidino indoles

An improved procedure for the synthesis of octahydroindoloquinolizine (1) from 3-(2-piperidino-ethyl)indole by oxidative cyclization process has been reported (392). 

Das ziemlich einfach herstellbare 1 -Hydroxy- 1-piperidino-cyclopropan kann in Gegen-wart von Titan(IV)-chlorid in einer Variante der Mannich-Reaktion als Aquivalent von Cyclopropanon/Piperidin dienen nach der anzunehmenden in-situ-Umwandlung in 1-Cyclopropyliden-piperidinium-chlorid erfolgen Reaktionen z.B. mit 1-Trimethylsiloxy-cyclohexen zu 2-Oxo-l-(l-piperidino-cyclopropyl)-cyclohexan (63%) und mit 1-Methyl-pyrrol bzw. Indol zu l-Methyl-2-( 1-piperidino-cyclopropyl)-pyrrol (65%) bzw. 3-(l-Pipe-ridino-cyclopropyl)-indol (84%)2 ... 

Indole derivatives have been prepared by reaction of 2-bromoanilines with enamines in the presence of palladium(II) acetate127, reductive cyclization onto a nitro group128, or by the same type of cycloaddition that allows the synthesis of benzofuranols (see above) but using / -quinone diimides129. An example of an application of this latter method is the regioselective nucleophilic addition of 1-piperidino-l-propene (245) to the selectively activated AT4-(phenylsulfonyl)-p-quinone diimide 244 (equation 51)130. Fur-... 

N-1 Aminoalkyl Chain A number of indole analogs bearing different aminoalkyl substituents at N-1 were synthesized (N-attached analogs, e.g., 34, Fig. 9) and tested (Eissenstat et al. 1995). This study found the aminoethyl substitution as an optimal requirement with morpholino, thiomorpholino, and piperidino analogs showing the highest activities. The respective acyclic amine and piperazine analogs were inactive. 

Since oxidized derivatives of secodine appear to be involved as late intermediates in the biosynthesis of the aspidospermidine and pseudoas-pidospermidine alkaloids, it is logical to begin with those secodine derivatives that have been found to occur naturally. Tetrahydrosecodine (1) occurs in the root bark of Aspidosperma marcgravianum Woodson (5) and has been detected in cell-suspension cultures of Rhazya stricta Decaisne (6) its demethoxycarbonyl derivative (2) also occurs in A. marcgravianum (5), and in Haplophyton crooksii L. Benson (7,8) and the roots of R. stricta (9). The two isomeric carbonyl derivatives, 2-ethyl-3-[2-(3-acetyl-V-piperidino)ethyl]indole (3) and crooksidine (4), occur, respectively, in A. marcgravianum (5) and H. crooksii (7,8). 

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