Octahydroindolo quinolizines

A new route has been developed for the efficient formation of the variably substituted indolo[2,3-a]quinolizine ring system, starting from a properly substituted 2-piperidone (103, 104). For the preparation of octahydroindolo-quinolizine (1), the unsubstituted 2-piperidone 139 was treated with triethox-onium tetrafluoroborate. Then the corresponding lactim ether 140 was alkylated with 3-chloroacetylindole followed by a subsequent two-step reduction process and Bischler-Napieralski ring closure. Finally, reduction of the C=N bond afforded ( )-l (104). 

Kametani and his collaborators presented two different approaches for the synthesis of ( )-yohimbine and ( )-p-yohimbine 223-226). The first one (223, 224) utilizes Stork s method for the Robinson reaction of the enamine derived from octahydroindolo[2,3-a]quinolizin-2-one (414) to produce 15,16-didehydroyohimbinone (410), prepared first by Szantay et al. (74, 221). 

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). 

The 13C shifts of the octahydroindolo[2,3-a]quinolizine [363] provide an important basis for the analysis of the 13C NMR spectra of the yohimbine and related group of alkaloids. The shifts shown in [363] (208) represent a revision of those originally made for C(9) and C(10) (225) since these were based on misassigned signals in the spectrum of indole itself (see Section XII.A). In addition, Wenkert (226) has suggested the interchange of the shifts for C(4) and C(6) and the correction has been made in [363]. 

C23H30Oy, 23637-79-8) sec Gestrinone cis-l-ethyl-l-(2-hydroxy-2-ethoxycarhonylethyl)-l,23,4,6,7,12,12b-octahydroindolo 23-o]quinolizine (C22Hk,N20, 43184-10-7) see Vinburnine 5- ethyI(2-hydroxyethyl)amino]-2-pentanone (C,2Hh,N02 74509-79-8) see Hydroxychloroquine 7-ethyl-3-(2-hydroxyethyl)indole (Ci2H,5NO 41340-36-7) see Etodolac... 

Octahydroindolo[2,3-a]quinolizin-2-one, a novel structure for i-ami-nobutyric acid (GABA) uptake inhibition. Eur. J. Med. Chem. 1985, 21, 151-154. 

The use of 521 led to the synthesis of a number of natural products through the aza-annulation of this (i-imino sulfoxide (Scheme 42).117 118 Application of methyl acrylate in this aza-annulation process led to the formation of 522. The chiral auxiliary was then used to provide moderate stereochemical control in the reduction of the enamide alkene to 523 and 524 in a 1.9 1.0 ratio. Compound 523 was then reduced to remove both the sulfoxide and the lactam carbonyl to give (-)-l,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine (525). 117,118... 

This latter substance [(— )-l,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]-quinolizine] has also been identified as the major alkaloid from Dracon-tomelum mangiferum (Anacardiaceae) (36). 

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