5-Coniceine

Evidence for a type of bound alkaloid emerged in the course of Fairbairn s studies on the distribution and variation in content of alkaloids in hemlock (Conium maculatum). The bound form is supposed to yield an alkaloid in the plant tissue upon hydrolysis. It may be possible that nucleotide-like compounds exist (see Section 6.4). 

The first paper of the series (Fairbaim and Challen, 1959) documented marked changes of alkaloid content during the period from the development of flowers up to the production of the mature fruits. Most striking were the variations in content of y-coniceine and coniine, which provided a hypothesis of actual interconversion of these two alkaloids (Fairbaim and 

The third paper of Fairbaim s series brings proof of existence of such substances in developing fruit (Fairbaim and Ali, 1968a). Three types of unidentified compounds have been separated on the basis of solubility in water, in 70% ethanol, and in pure ethanol. Upon hydrolysis by acid or alkali, all three groups of compounds yielded Dragendorff-positive substances. Some were not identified, but coniine and y-coniceine were positively detected. 

Radioactive y-coniceine fed to plants bearing maturing fruit was rapidly deposited into the fruit, and the radioactivity could be recovered as bound and free forms of not only y-coniceine itself but also of coniine. The same occurred after administration of radioactive coniine (Fairbaim and Ali, 1968b). Specific radioactivities of bound forms of alkaloids fluctuated. This is regarded as indicating the involvement of bound alkaloids in important metabolic processes. On the contrary, free coniine and y-coniceine retained their specific radioactivity essentially unchanged even after 19 

A comparison of the total activity ratios (since all three compounds were recovered to the same extent) is indicative of the relative turnover of these three compounds the total activity ratios y-coniceine coniine N-methylconiine were 1770 1 1 at 4 hr, 165 26 1 at 11 hr, and 80 40 1 at 35 hr. These ratios indicate that y-coniceine is not turning over faster than coniine, nor the latter faster than its methyl derivative, and that y-coniceine is not being converted into other compounds at rates which compare with its conversion into coniine. 

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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... 

The Coniceines, CgH jN. Six of these products have been obtained in various ways from the two conhydrines. Their chief characteristics are tabulated below. oL-Coniceine is perhaps the least well-defined of the six it is one component of the mixture resulting from the action of hydrochloric acid on conhydrine, and is described by Loffler (1904) as stereoisomeric with e-coniceine (II). 

P-Coniceine is the chief product of the action of phosphoric oxide on conhydrine and was shown by Loffler and collaborators to be 2-propenylpiperidine, CjHgNH. CH CH. CHg. 

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). 

Conditioning chamber la 87,129,131 y-Coniceine 15188 Coniferyl alcohol 15 401 Coniine 15 188... 

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). 

Indolizidine is the alkaloid S-coniceine and this nucleus has been observed in several groups of alkaloids. Since the chemistry of alkaloids deriving from indolizidines and partially unsaturated indolizidines is reported regularly (B-81MI30800, B-79MI30800), only selected examples will be taken from the natural products field. Structurally more complex alkaloids such as (217), (218) and indolizidine aza steroids (81H(16)1093,81H(16)1097), which may often be assigned to other groups of alkaoids as well, are not mentioned. 

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. 

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