A-Coniceine

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). 

Coniceine (Hofmann s a-coniceine) is obtained by the action of sulfuric acid on bromoconiine (132). It is a fully saturated tertiary base... 

Of the total alkaloids of hemlock isolated by the method of Chemnitius and fractionally distilled, the portion boiling up to 190° contains most of the coniine, -y-coniceine and A -methylconiine, the eonhydrine and... 

The preparation of Z-coniinc by the reduction of -coniceine (Z-propenylpiperidine, j). 20) by Loiller and Friedrich is interesting as a... 

Constitution. On oxidation with chromic acid, conhydrine yields Z-piperidyl-2-earboxylic acid. It is converted into Z-coniine either by reduction of the iodo-derivative (iodoconiine), C,HijNI, formed by the action of hydriodic acid and phosphorus at 180° or by hydrogenation of the mixture of coniceines produced, when it is dehydrated by phosphorus pentoxide in toluene. These and other observations indicate that the p- ygen atom must occur as a hydroxyl group, in the w-propyl side-chain in either the a- (XV) or (XVI) position, since the y-position would involve... 

S-Coniceine (2-piperolidine), is prepared by the action of sulphuric acid on bromoconiine. It has a multiplicity of names. Itw, s first characterised by Lellmann, who assigned to it formula (III) and was synthesised by Loffler and Kaim who distilled piperidylpropionic acid to obtain piperolid-2-one (IV) and reduced this to 2-piperolidine (III) which proved... 

The piperideine derivatives have not been studied as extensively as the analogous pyrrolines (151,152). The imino structure has been established, for example, for the alkaloid y-coniceine (146) (46). The great influence of conjugation on the structure is seen with l-(a-picolyl)-6,7-methylenedioxy-3,4-dihydroisoquinoline (47), possessing an enamine structure, whereas the analogous 1-methyl derivative (48) possesses an imine structure according to infrared spectra (152,153). 

Figure 2.2 Three piperidine alkaloid teratogens from Conium maculatum (poison-hemlock) (a) coniine, (b) y-coniceine, and (c) A-methyl coniine, with accompanying LD50 as determined in a mouse bioassay.

Pharmacologically, the properties of all three alkaloids are very similar, except y-coniceine is more stimulatory to autonomic ganglia and VV-methyl coniine has a greater blocking effect (Fodor and Colasanti, 1985). 

Piperidine alkaloids such as coniine and (—)-coniceine are very poisonous. They occur in hemlock (Conium maculatum L.), known as a very toxic plant. One of the characteristics of these piperidine alkaloids is smell. Moreover, they are neurotoxins which have acute effects such as chronic toxicity. 

Communesin alkaloids 136 Communesin G 56, 136 Communesin H 56 Condaline 157 Condaline A 157 Conessine 10, 42 Coniceine 10... 

Azacyclanones,2 The usual syntheses of medium-sized azacyclanones involve Dicckmann or acyloin cyclization conducted under high dilution. An interesting new approach involves hydroboration-cyanidation (4, 446-447 5, 606-607) of a diunsaturated carbamate such as 1. llydroboration of I with thexylboranc followed by cyanidation under standard conditions gives the cyclic ketone 2 in moderate yield in one step. The product can be rcductivcly cyclizcd to the indoliz.idinc alkaloid 5-coniceine (3). 

The perhydroindolizine, named indolizidine, is the alkaloid <5-coniceine. There is a great number of indolizidine alkaloids. Since the chemistry of these alkaloids is reviewed regularly (see Sections 3.08.4 and 3.08.6 for references), only selected topics from the natural products field will be treated here. 

A synthesis of 5-coniceine by a transannular reaction has been reported (81TL2075). Treatment of N-allyl-N-3-butenyl-N-benzyloxycarbonylamine with thexylborane followed by cyanidation afforded an azacyclanone in 35% yield which could be transformed into 5-coniceine by catalytic reduction (Scheme 28). 

The indolizines constitute the core structure of many naturally occurring alkaloids, such as (-)-slaframine, (-)- dendroprimine, indalozin 167B and coniceine. There are a number of different routes to the synthesis of indolizines and they are most commonly synthesised by sequential N-quaternisation, intramolecular cyclocondensation reactions or the cycloaddition reaction of /V-acyl/alkyl pyridinium salts. 

The recent synthesis of ( ) 8-coniceine (190) involved a pyrroline derivative (191) as a key intermediate as it was relatively stable. It was cyclized with methanolic hydrogen chloride, desulfurized with Raney... 

The seco-phenanthroindolizidine alkaloid septicine has been synthesized by a nitrone route. A cycloaddition of 1-pyrroline 1-oxide with 2,3-bis-(3,4-dimethoxyphenyl)butadiene gives two stereoisomeric isoxazolidines, one of which is converted into ( ) septicine.10 ( )-Tylophorine and 5-coniceine have been prepared by a new route that makes use of an intramolecular imino-Diels-Alder reaction.11 A stereoselective synthesis of 3,5-dialkyl-indolizidines has been applied to the synthesis of a stereoisomer of the trail pheromone of the Pharaoh ant and to a stereoisomer of gephyrotoxin 223.12 A stereoselective total synthesis of ( )-perhydrogephyrotoxin (21)13 and a simple synthesis of ( )-gephyran14 have been reported. 

A situation analogous to that of the pyrroline derivatives also exists, according to spectroscopic data, with N-unsubstituted piperideine compounds. There is little experimental data because A 2-piperideines have not been studied as extensively as the analogous pyrrolines. The A structure has been established for some aliphatically substituted piperideines, e.g., J1(8)-hexahydropyrindene,12,13 J1(10)-octahydro-quinoline,13 and the alkaloid y-coniceine.14,15 According to conformational considerations, structures other than A piperideine could be expected more frequently in the piperideine series. The thia analog16 3 occurs in the amino form as shown by infrared spectral data and the estimation of active hydrogen. 

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