Pseudoconhydrine

Hydroboration preferentially gives the 2,5-tmns isomer resulting from the attack of a borane from the less hindered side of a molecule, and hydroboration does not proceed to the trialkyl borane stage. Further elaboration of these alcohols afforded (3-hydroxypiperidine alkaloids such as racemic pseudoconhydrine 120, racemic A -methyl pseudoconhydrine 121, and (—)-5-hydroxysedamine 122. 

A convenient method to affect the oxidation p- to nitrogen in piperidines is based on the anodic oxidation of N-carboalkoxy piperidines (Scheme 35). The electrochemical oxidation of piperidine (152) in the presence of acetic acid and potassium acetate, for example, afforded a mixture of isomeric 2-hydroxy-3-acetoxypiperidines (153) in a combined yield of 93%, following an aqueous workup [61]. Reduction with sodium boro-hydride severed the C-OH bond. Treatment with acid and then base completed a synthesis of pseudoconhydrine (154). 

These reactions proceed via the a-acetoxy derivative, which then forms the en-amide. Furfrier oxidation of the enamide gives the isolated products. A synthesis of cu-pseudoconhydrine 29 from 2-propylpiperidine illustrates both this process and also the regioselectivity in oxidation of amides, which favours attack on a methylene rather than a methine carbon atom [126],... 

Interestingly, the anodic oxidation of N-methoxycarbonylpiperidine derivatives 41 in AcOH affords 2,3-diacethoxylated products 42. This reaction is conveniently applicable to the synthesis of Conium alkaloids such as pseudoconhydrine 28). 

In a variation on the two-component cycloaddition reaction, a [3+3] strategy was reported whereby reaction of enantiomerically pure aziridines, generated from amino acids, with palladium trimethylenemethane complexes leads to a piperidine (Scheme 114). Yields ranged from 63% to 82% and the efficiency of the methodology was demonstrated by the four-step synthesis of (—)-pseudoconhydrin <2001SL1596>. 

Conium maculatum (hemlock) contains the poisonons piperidine alkaloid, coniine, and related alkaloids, N-methyl-coniine, conhydrine, pseudoconhydrine, and gamma-coniceine. It has well-established teratogenic activity in certain animal species. 

One of the hemlock alkaloids, ( )-pseudoconhydrine (261), was synthesized from the halomethylpyrrolidine derivative 258, based on the reported... 

Thus slow addition of 1 equiv of trifluoroacetic acid to 259 at room temperature furnished material that contains 85% of the piperidine 260 according to NMR analysis. Finally, solvolysis of the trifluoroacetyl group of 260, using potassium carbonate in methanol, gave ( )-pseudoconhydrine (261) (Scheme 51). 

It shows a strong similarity to some of the Cassia-type bases. Several stereoselective syntheses of pseudoconhydrine have been reported (T. Shono et al., Chem.Letters, 1984, 1101 1129 G.VJ.J. Fleet, M.J. Gough and P.VJ. Smith, Tetrahedron Letters, 1984, 25, 1853). ( )-a-Conhydrine (76)... 

A recent synthesis of pseudoconhydrine (165) and A-methylpseudoconhydrine (166) utilized an osmium catalyzed asymmetric dihydroxylation of an A-alkenylurethane derived from L-norvaline [438]. 

Of the alkaloids belonging to this group, neither conhydrine nor pseudoconhydrine had ever been synthesized. Syntheses of both have now been published, together with further work concerning 8-coniceine. 

Pseudoconhydrine was assigned the structure of 5-hydroxy-2- -propyl-piperidine in 1935 (35). Many years later, it was synthesized simultaneously in three different laboratories. In one synthesis... 

Comum Fruit, Hemlock poison hemlock spotted hemlock poison parsley spotted cowbane, Full-grown, but unripe, carefully dried fruit of Conium maculatum L., Um-belUferae. Habit. Europe, Asia, naturalized in U.S. Constit. 0.5 15% coniine, conhydrine, pseudoconhydrine, methyl-coniine, ethylpi peri dine, comic acid, volatile and fixed oil. Has antispasmodic activity. 

Schorm (109) recommended fractional distillation for the separation of the remaining hemlock alkaloids, but this has been shown to be insufficient. According to Wolffenstein (110) the fraction, b.p. 173-174°, contains mostly iV-methylconiine with a little coniine which is separated either by nitrosation or by fractional crystallization of the hydrobromides. The 7-coniceine contaminated with coniine is contained in the fraction, b.p. 169-173°, and the two bases are separated by making use of the different solubilities of their hydrochlorides in acetone. A method for the quantitative separation of the bases has been outlined by v. Braun (112) which involves fractional distillation to remove most of the lower boiling coniine. The minor alkaloids are in the next fraction, while conhydrine and pseudoconhydrine are left in the residue. The minor alkaloids are benzoy-lated and the tertiary A-methylconiine separated. 7-Coniceine is obtained by fractional distillation of the benzoylated mixture and saponification. 

Hofmann (130) has described three methods for the preparation of a-coniceine, but these yield different products. The action of fuming hydrochloric acid on conhydrine produces the tertiary base a-coniceine, whereas the effect of alkali on iodoconhydrine and that of sulfuric acid on bromoconiine produce -coniceine and 5-coniceine respectively (132). If, on the other hand, bromoconiine is treated with alkali, y-coniceine is obtained. /3-Coniceine is the main product of the dehydration of conhydrine with phosphoric anhydride and pseudoconiceine is obtained as a product of the dehydration of pseudoconhydrine (191). 

Pseudoeoniceine is a product of the dehydration of pseudoconhydrine with phosphoric anhydride (191). It is a strongly basic, colorless oil, b.p. 171-172°, d4 0.8776, [ ] + 122.6°, which forms salts (Table 3). It reduces potassium permanganate readily and on treatment of its hydrochloride with nitrous acid gives rise to a nitrosoamine so that it is an unsaturated secondary amine. It readily absorbs hydrogen iodide with the formation of an iodoconiine hydriodide, m.p. 182°, which is different from the derivative obtained by the direct action of fuming hydriodic acid on pseudoconhydrine since the hydriodide of the latter melts at 216-217°. Pseudoeoniceine when reduced either via its iodo derivative (191) or... 

In a synthesis of the alkaloid (-)-pseudoconhydrine [(-)-G] the following reactions were carried out starting from (5)-proline (X) ... 

A general method for the preparation of piperid-3-ols has been adapted to the biogenetic-type synthesis of pseudoconhydrine (40) (Scheme 3). Of the two... 

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