Pelletierine, synthesis

In the case of protein amino acid-derived alkaloids, the second obligatory intermedia is synthesized from the obligatory intermedia by chemical reactions. In the pelletierine synthesis pathway started with L-lysine, the second obligatory intermedia is A -piperidinium cation. It is formed by a Maimich reaction from A -piperidine (obligatory intermedia) and COSCoA. The second obligatory intermedia, by hydrolysis decarboxylation, produces pelletierine. 

The following synthesis of p ewdopelletierine is of special interest, since it involves only materials and conditions which could occur in plants and is therefore a possible bio-synthesis. Menzies and Robinson showed that when calcium acetonedicarboxylate, glutardialdehyde and methyl-amine are mixed in aqueous solution under specified conditions and the mixture is kept for twenty-four hours, a produet (XX) is formed, which can be decarboxylated to -pelletierine (XXI) and the latter isolated as the picrate, whieh after recrystallisation yields the pure base (m.p. 48-5°), the identity of which can be established by eonversion to the characteristic dipiperonylidene derivative. The course of the synthesis is represented as follows — ... 

Pelletierine and associated bases, pharmacological action, 62, 108 isoPelletierine, 55, 57, 58 pserwfoPelletierine, 55, 58 constitution, 59 synthesis, 61 Pellitorine, 2... 

Figure 49. Diagram of the pelletierine, lobelanine and piperine synthesis pathway.

Myrtine and 4-epimyrtine were obtained from Vaccinum myrtillus 110). The structure of myrtine (60) and the absolute configuration at C-4 (R) and C-10 (R) were established on the basis of IR and H-NMR spectra. Synthesis was accomplished from (/ )-(-)-pelletierine (61) and acetaldehyde (Scheme 1) 111). Racemic myrtine (60) and 4-epimyrtine (64) were also obtained by the method of Scheme 1. 

An improved synthesis of myrtine (23) from ( )-pelletierine (21) has been reported (Scheme 3) (c/. Vol. 9, p. 71). Stereospecific addition of methyl-magnesium iodide to the cyclic enaminone (22) gave ( )-myrtine, which was converted into natural (+)-myrtine by resolution with (-)-tartaric acid.31... 

The synthesis of 54 was similarly performed from 2-bromoveratraldehyde (166), methyl 4-hydroxycinnamate, and pelletierine. The product was shown to be identical to the natural alkaloid and the structural assignment was confirmed (42). 

Decinine (2) was prepared similarly by Lantos and Loev (80), from the biphenyl aldehyde (169). Calcium hydroxide-catalyzed condensation with pelletierine afforded biphenyl quinolizidone (172) in 20% yield. This compound was obtained in better yield from the acid-catalyzed epimerization of the cis-fused diastereomer (173) of the decamine synthesis (68). 

A new convenient synthesis of pelletierine (18) has been reported it is outlined in Scheme 2.20... 

A synthesis of pelletierine (169) was reported, based on the reaction of 2-hydroxypiperidine carbamate with a carbonyl-stabilized Wittig reagent [442]. 

The alkaloid (93) which is produced by Haloxylon salicornicum shows a structural resemblance to pelletierine (89). A feeding experiment58 with [6-14C]-lysine in intact plants has supported the related biosynthesis in Scheme 18. Activity was incorporated at C(6) of the alkaloid as shown. Surprisingly, no activity was incorporated from [2-14C]acetate but this negative result could be due to the failure of acetate to reach the site of synthesis. 

Five alkaloids have been reported as occurring in the bark of the pomegranate tree. Of these, isopelletierine, methylisopelletierine, and pseudopelletierine have been assigned satisfactory structures which have been confirmed by synthesis. The other two are pelletierine and methylpelletierine, and as already reported in Volume I, the occurrence of the latter is uncertain. Pelletierine was assigned the structure of /3-(2-piperidyl) propanal (4). Numerous attempts to synthesize a compound of this structure have failed (5-11). Although it is possible to isolate a derivative of the aldehyde, /3-(2-piperidyl) propanal itself could not be obtained. This long series of failures has raised doubts as to the existence of pelletierine or, at least, as to the correctness of its assigned structure. 

Earlier syntheses of quinolizidines involved Mannich reactions of pelletierine. In a new approach, applied to the synthesis of (+)-vertaline (Scheme 6), allylic strain controls the stereochemical course of cyclisation of the N-acyliminium ion (40) the... 

An elegant synthesis of pelletierine acetal has been reported (497) although it has not yet been possible to synthesize the alkaloid itself. /3-(2-pyridyl) - propionaldehyde diethylacetal, obtained in 28-29% yield from lithium picolyl and bromoacetal, is hydrogenated in glacial acetic acid over a platinum catalyst to 3-(2-piperidyl)-propionaldehyde diethylacetal. It is of interest to note that if the hydrogenation be carried out in dilute solution, the product is 6-coniceine (498). However, hydrolysis of the acetal succeeds only if the secondary nitrogen is first blocked (497, 518). 

In the course of a study of a synthesis of dZ-pelletierine, Beets and Wibaut (498) discovered a new mode of preparation of 5-coniceine. The catalytic hydrogenation of j8-(2-pyridyl)-propionaldehyde diethyl acetal in glacial acetic acid solution over platinum leads to different products, depending on the concentration used. If the hydrogenation be carried out in concentrated solution, the product is dZ-pelletierine diethyl acetal, but if a dilute solution is used, 5-coniceine is obtained. Solutions of medium concentration afford mixtures of the two products. 

The pH dependence of the synthesis of pelletierine from J -piperideine and acetoacetic acid has been investigated (17,18). Pelletierine has been synthesized from cadaverine and acetoacetic acid in the presence of diamine oxidase (19). Pelletierine has recently been isolated from Duboisia myoporoides R.Br. (20), Sedum acre L. (21), and Withania somnifera Dunal (22). 

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