Indolo quinolizine alkaloid

The simplest member of the indolo[2,3-a]quinolizine alkaloid group has been found in Dracontomelum magniferum Bl. (II) it possesses structure (—)-l. No name has as yet been given for this levorotatory alkaloid. 

Didehydrogeissoschizine (147) has been proposed to be the biogenetic precursor of simple indolo[2,3-a]quinolizine alkaloids such as flavopereirine (148)... 

Ortho lithiation of 2-substituted indoles occurs readily, but fragmentation to an alkynylanilide may occur in some instances. The use of a 2-pyridyl group to facilitate the 3-lithiation of an indole was recently used in a synthesis of some indolo[2,3-a]quinolizine alkaloids an example is the synthesis of flavopereirine (22 Scheme 29). 

Several other groups have made use of the Smith indole synthesis, and a summary of this work is shown in Table 1. Gribble and cowoikers prepared 2-(2-pyridinyl)indoles en route to syntheses of several zwitterionic indolo[2,3-fl] quinolizine alkaloids (Entry 1) [13], and Husson and Hashimoto synthesized a derivative of the alkaloid goni-omitine via a Smith indole synthesis (Entry 2) [14]. Henegar and Hunt reported a very convenient synthesis of 2-trifluoromethylindole (Entry 3) [15], in which TMEDA was found to be necessary. Two bis-indoles were prepared in low yield (Entry 4), bnt this approach failed for n = 1 [16], The bridged indole shown in Entry 5 was synthesized following acid-catalyzed cyclization of the initially formed indole [17]. 

Dihydrocorynantheol (21), first isolated from Aspidosperma marcgravianum (147), is the simplest corynanthe alkaloid. The members of this type of alkaloid have three stereo centers in the D ring of the indolo[2,3-a]quinolizine skeleton. This substitution pattern allows four possible relative arrangements for the C-3, C-15, and C-20 stereo centers, the names of which are normal, pseudo, alio, and epiallo, respectively. 

Results and data gathered on mass spectroscopy of various indole alkaloids have been summarized by Hesse (320). The derivation of the characteristic fragments of indolo[2,3-a]quinolizidines has been interpreted by Gribble and Nelson (321), who investigated C-3, C-5, C-6, C-20, and C-21 deuterated derivatives of octahydroindolo[2,3-a]quinolizine (1). Kametani et al. have observed and proved, with labeled compounds, a methyl transfer from the ester function of reserpine derivatives to the basic nitrogen atom during mass-spectroscopic measurement (322). 

Often indolo[2,3-fl]quinolizines (e.g., 109) form the skeletal basis for work in the indole and oxindole alkaloid field. These are most often prepared from pyridinyl- (108) or quinolinylindolethanes via reduction with metal hydrides. The tetrahydropyridines then undergo acid-catalyzed ring closure, often giving mixtures of several compounds (109,110, 111). 

In this section are described the syntheses of some simple indolo-[2,3-a]quinolizine derivatives which bear a close relationship to the alkaloids of the yohimbane and corynane groups. 

Johns SR, Lamberton JA, Occolowitz JL. 1,2,3,4,6,7-Hexa-hydro-12H-indolo[2,3-a] quinolizine, an alkaloid from Dra-contomelum mangiferum BI. (family Anacardiaceae). Aust. J. Chem. 1966 19(10) 1951-1954. 

---