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A method is described for the efficient preparation of 3-amino-Δ5-piperidein-2-ones3. A synthetic application of enamides 3 has been achieved by methylthiolation on the C5 position to obtain the target methionine-derived pseudopeptides 2.

17-Azaeburnamine type compound 2 is synthesized by closure of ring E on 1-aminoindolo[2,3- a ]quinolizidine 8 . Compound 8 is obtained by a Neber rearrangement on the corresponding indolo[2,3- a ]quinolizidin-2-one, or by K t BuO cyclisation of 3-amino-2-(2-indoly)piperidin-4-one 16 . In both cases the starting substrate is 4-piperidone 3 . The synthesis of the new [ABED] ring system 6 is also described.

(αR, 3RS, 5S)-3-Amino-N-(2-hydroxy-1-phenylethyl)-5-methylthio-2-piperidones1 have been synthesized from enamide 2 by subsequent free radical addition of methanothiol on position 5 and amination of 3-position.

20-Epidasycarpidone ( 10 ) and its N -benzyl analogue 9 have been synthesized via a conjugate addition of 2-(1,3-dithian-2-yl)indole ( 6 ) and 3-ethyl- Δ 3 -piperidein-2-ones 7 and 8 , respectively. The transformation of 20-epidasycarpidone to 20-epiuleine ( 11 ) has been carried out as described in the literature in order to corroborate the structural assignments.

The synthesis of asymmetric 2-indolyl-4-methylenepiperidines 8–11 and 14–15 by condensation of an aminoallylsilane with an indole carbaldehyde, followed by intramolecular cyclization of the intermediate, is described. The reactivity of N-(2-hydroxyethyl)indolylpiperidines 9 and 14 with KtBuO to give indolo[2,3-a]quinolizidines is studied. Some unexpected results are obtained due to the influence of the α-phenyl ring.

The effect of the N.N-diethylcarbamoyl indole protecting group on the reactivity of 2-(1,3-dithian-2-yl)indole 7 in front of a series of electrophiles, as well as the potential synthetic usefulness of the resulting 2,2-disubstituted dithianes is reported.

The synthesis of indolo[2,3-α]quinolizidin-2-one (1a) has been accomplished by the direct cyclization of N-hydroxyethyl-2-[1-(phenylsulfonyl)-2-indolyl]-4-piperidone ethylene acetal (4) with KtBuO. Nevertheless, treatment of the 3-ethylpiperidine analogue 16 with KtBuO only led to the corresponding hexahydro-4H-pyrido [1',2':1,2]pyrazino [4,3-α]indole (23), resulting from the cyclization upon the indole nitrogen.

A new synthetic route to indolo [2,3-g]morphans and 7,8-benzomorphans is reported. The key step in these syntheses is the mercuric acetate oxidation of appropriate 2-(4-piperidylmethyl) indoles or 4-benzylpiperidines, respectively. An alternative synthetic entry to 2-(4-piperidylmethyl)indoles, consisting in Wadsworth-Emmons condensation of a suitable 4-piperidone with diethyl 2-oxopropylphosphonate followed by catalytic hydrogenation and Fischer indolization of the resulting 4-acetonylpiperidine, is described.

A new synthesis of 9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzo aquinolizin-2-one ( 1a and its 3-ethyl derivative 1b via the corresponding 2-(3,4-dimethoxyphenyl)-4-piperidone ethylene acetals 7 is reported. Alkylation of 2-arylpipendires 7 with 2-bromoethanol followed by oxidation of the resulting amino alcohols 9 with oxalyl chloride and dimethyl sulfoxide afforded the aldehydes 10 , which were cyclized with hydrochloric acid to give 7-hydroxybenzo[α]quinolizidines 11 . The reduction of 1 with trinethylsilane and subsequent acid hydrolysis led to benzo aquinolizidin-2-ones 1 .