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A molecule with an indole skeleton, containing a latent acrylic ester function—acting as a diene—readily reacted with benzoic acid (4-bromomethylene-5-oxo)hexyl ester that had been built up from pentane-2,4-dione. Dehydration of the enamine and subsequent [4+2] cycloaddition supplied epimers having the d -secoaspidospermane skeleton. These compounds directly or after epimerization gave (±)-minovincine. Oxidative ring transformation of (±)-minovincine under different conditions led to (±)-16-acetyl-16-deethylapovincamine and (±)-vincaminine.

A molecule with an indole skeleton, containing a latent acrylic ester function—acting as a diene—was produced from Nb-trityl-2-(hydroxy-methyl)-tryptamine and reacted with esters containing an aldehyde or aldehyde-equivalent structural unit, yielding 3-oxo-16,17-dihydro-Δ20-secodin-17-ol type intermediates from which dehydration, followed by [4+2]cycloaddition, furnished 3-oxovincadifformine and 3-oxominovincine. We also wished to apply the method to produce 15β-hydroxyvincadifformine, however, the appearance of a dimeric product with indole skeleton was observed instead of the expected cycloaddition.

The first syntheses of the alkaloids (−)-mehranine (3), (+)-voaphylline/conoflorine (4), (+)-Na-methylvoaphylline/hecubine (5), and (−)-lochnericine (2) were achieved by stereoselective epoxidation starting from (−)-tabersonine (1), through intermediates with the aspidospermane and quebrachamine skeleton.

The oxidation of (-)-tabersonine (1) with dimethyldioxirane (DMD) in neutral and acidic medium gave 16-hydroxytabersonine-N-oxide (3) and the didehydrovincamine isomers 4 and 5, respectively. (+)-14,15-Didehydro-quebrachamine (7) furnished the hydroxyindolenine 9, and the pentacyclic derivative 11. (+)-Quebrachamine (8) and DMD in neutral medium gave (7S,20S)-(+)-rhazidigenine (12) which was converted to (2R,7S,20S)-(+)-rhazidine (13b) with hydrochloric acid.

The reaction of enamines 4a, b with acrylonitrile gave rise to compounds 6a, b in addition to four ( 7a–10a and 7b–10b ) stereoisomeric derivatives of a new heterocyclic ring system, the structures of which were thoroughly investigated by different spectroscopic methods, in particular by C NMR. Molecular structures of 7a–10a were substantiated by single crystal X-ray diffraction. Crystal data were collected on a CAD-4 diffractometer using monochromatic CuKα radiation (λ = 1.541 80 A) and the model structures determined by direct methods were refined on F 2 values. The conformations of the four diastereomeric molecules are rather similar. The epimerization at C(12) has only a slight effect on the bond angles around the bridge head atom, while the exchange of the -C 2 H 5 and -C 2 H 4 CN functions has practically no impact on the bond lengths, bond angles and torsion angles around C(1). The excellent internal consistency of the molecular geometry permitted characterization of the bond lengths of C(sp 3 )-X (X  C(sp 3 ), C(aryl), C(sp), etc.) types.

Using our previously reported convergent synthetic strategy, secondary amine, methyl 2-[3-(2-[benzylamino]ethyl)indol-2-yl]-3-hydroxypropionate (6), and aldehyde, ethyl 2-ethyl-4-formylbutanoate (9), reacted to give tetracyclic esters ,pyrrolo[2,3-d]carbazole derivatives 10 and 11, which readily led to pentacyclic lactams indolizino[8,1-cd]carbazole derivatives 14-16. Selective reduction of these products gave (±)-pseudovincadifformine (4), (±)-20-epipseudovincadifformine (5), and (±)-14-epipseudovincadifformine (20). 2-ethyl-4-formylbutyl benzoate 23 was also prepared and could be directly used for synthesizing (±)-20-epipseudovincadifformine (5). The introduction of the double bond into ring D of the pseudoaspidospermane skeleton was successfully achieved to obtain 21-oxopseudotabersonine (30)

Compound 3, which has an indole skeleton containing a masked acryl ester function, was synthesized from the hydrochloride of 2-(ethorycarbonyl)tryptamine (2). The cycloaddition of 3 with methyl 4-formylhexanoate (21) or with 5-(benzoylocy)-2-ethylpentanal (33) yielded the starting materials for beget compounds (±)-vincadifformine (4), (±)-3-oxotabersonine (42), and (±)-tabersonine (43). The synthesis of vincadifformine (4) was achieved in two different ways: via 3-oxovincadifformine (7) and via tetracyclic benzoate esters 37 and 38. The double bond requiredin tabersonine (43) and 3-oxotabersonine (42) was introducedby treatment of 3-thioxovincadifformine (39) with p-toluenesulfinyl chloride

L'intermediaire commun est l'ethyl-1α octahydro indolo [2,3-a] quinolizinemethanol-1β; etude RX d'un derive de methano-3,7azecino [5,4-b] indole

The tryptamine derivative 1 readily reacted with methyl 4-acetyl-5-bromopent-4-enoate (9) that had been built up from 2,4-pentanedione. On intramolecular dehydration and subsequent [4 + 2] cycloaddition, the reaction product 10 gave the epimers 12 and 13 having the d-secoaspidospermane skeleton. Compound 12 directly and 13 after epimerization yielded (±)-3-oxominovincine (14). Regioselective reduction of 14 furnished (±)-minovincine (17).

Preparation des composes du titre a partir de (±)-eburnamonine et de son epimere en 3; la reaction de leurs mesylates avec NaCN conduit aux epimeres de l'ethyl-1 octahydro indolo [2,3-a] quinolizinepropriononitrile-1