A new method for the synthesis of trans-2,6-disubstituted piperidine derivatives is described. The transformation of cyclic α-methoxycarbamates 5 and 6 affords trans ketones 17 and 18. The synthesis of diols 1–4 from 17 and 18 has shown that the structure proposed in the literature for the piperidine alkaloid andrachamine is incorrect. A reexamination of the original spectral data of this alkaloid suggested that it is a meso 2,6-disubstituted piperidine derivative. Unambiguous syntheses of 23 and 24 and comparison with a sample of andrachamine have established that this alkaloid possesses structure 23. Key words: N-acyliminium, piperidine, alkaloid, andrachamine.

Two new 2,6-disubstituted piperidine alkaloids andrachcinine (1) and andrachcinidine (5) have been isolated from Andrachne aspera along with andrachamine and andrachcine (2). The absolute configurations of 1, 2, and 5 were established. (+)-Allosedridine and the new alkaloids (-)-8-epi-8-ethylnorlobelol I (4) and (-)-8-epihalosaline (7) were also identified as constituents of A. aspera. Structures were determined by MS and NMR techniques and by chemical conversions.

. 72, 1347 (1994). The cycloaddition reactions of 3,4,5,6-tetrahydropyridine I-oxide 1 with the homochiral alkynyl sulfoxides 60-e proceed in high yield to afford, with low asymmetric induction, mixtures of diastereomeric isoxazolines that are readily separated by column chromatography. ' The resolved isoxazolines can be subsequently converted, by hydrogenolysis, to enantiomeric p-amino ketones.CHANTAL LOUIS, SIBEL MILL, VINCENT MANCUSO et CLAUDE HOOTEL~. Can. J. Chem. 72, 1347Chem. 72, (1994. Les rCactions de cycloaddition entre la 3,4,5,6-tktrahydropyridine I-oxyde 1 et les sulfoxydes acCtylCniques homochiraux 6a-e conduisent avec de bons rendements et une induction asymetrique faible a des mtlanges d'isoxazolines diasttrtoisom&res facilement sCparables par chromatographie sur colonne. Les isoxazolines rCsolues peuvent &tre converties, par hydrogtnolyse, en p-aminocCtones Cnantiomkres.[Traduit par la RCdaction] Introduction ene (6) (Scheme 2). Based on the fact that Grignard reactions p -~~i~~ ketones an important ,-lass o~c o m p o u n~s with chiral sulfinate esters proceed stereospecifically with for which the synthesis deserves interest. In this regard, we preinversion of configuration at the sulfur atom (7), the acet~lenic viously reported a new efficient synthesis based on the observasulfoxides 6a-e are assigned the S configuration; the optical tion that 4-isoxazolines 3 can be viewed as masked p-amino purity and the absolute configuration of 6c-e were previously ketones, which could be released by hydrogenolysis of the confirmed by their conversion into the corresponding alkenyl N-0 bond (1) (Scheme 1). Although 4-isoxazolines have derivatives (6).2 proven to be thermally labile heterocycles and display an arrayThe reaction nitrone 1 with the alkynyl sulfoxides 6a-e of rearrangements (2, 31, we established that under carefully gave mixtures of the diastereomeric isoxazolines 7a-e and 8a-e controlled conditions they can be prepared in good yield by (Scheme 3); the large differences in the R,s allowed the comnitrone-alkyne cycloaddition. ~~~~~~~ of the N-0 plete separation of the individual diastereomers of each pair by bond can be performed by hydrogen in the presence of P d C .flash chromatography silica gel. Typical results are PreApplication of this procedure to the synthesis of sented in and deserve some 2-phenacylpiperidine, for example (4, R = C6H,), proceedsAll the cycloadditions proceed with excellent yields. It from nitrone 1 and pheny lacety lene with 70% overall yield. In

The piperidine alkaloid (+)-8-ethylnorlobelo-I is assigned the revised 2S,8S absolute configuration as depicted in 7. LiAl(O-tBu)3H reduction of the ketone rac-5 proceeded with a high stereoselectivity to give, after hydrolysis of the carbamate function, the s y n amino alcohol rac-6. Inversion of the C-8 configuration of ent-6 yielded (-)-8-ethylnorlobelol-I ent-7. A short nitrone-alkene-based synthesis of rac-7 has been developed.

A Revised Structure for the Piperidine Alkaloid Andrachamine (XIV). -Unambiguous synthesis establishes that andrachamine has structure (XIV) and not (XV) as was proposed earlier. -(MILL, S.; HOOTELE, C.; Can.