Isopelletierine

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

In the six-membered series the alkaloids of Punica gr ana turn, isopelletier-ine and methylisopelletierine, have been obtained by treatment of enamines with acetoacetic acid. Isopelletierine (194, R = H) was prepared also by Schopf et al. from d -piperideine (309-311). The reversibility of aldol dimerization (124,131) of enamines has been established by the synthesis of methylisopelletierine (194, R = Me) from dimethyltetrahydroanabasine, accomplished by Lukes and Kovaf (101) (Scheme 19). 

Punica granatum L. Shi Liu Pi (Pomegranate) (pericarp, root bark) Pelletierine, isopelletierine, methylisopelletierine, methyl-pelletierine, pseudopelletierine, gallotannic acid, sitosterol, ursolic acid, maslinic acid, elegic and gallic acid.33-450 This herb is toxic. Purges intestinal parasites. 

Sedum sarmentosum Bunge. Chui Pen Chao or Jing Tian (Stringy stonecrop) (whole plant) Sarmentoslin, dihydro-N-methyl-isopelletierine, N-methyl-2-((3-OH-propyl) piperidine, N-methyl-isopelletierine, dl-methylisopelletierine, dihydroisopelletierine.33-48-50 Antipyretic, detoxicant, diuretic, treat hepatitis. 

Punica granatum L. China Pelletierine, isopelletierine, methyl-pelletierine, methylisopelletierine, pseudopelletierine, tannic acid, granatin.33 This herb is toxic. Treat intestinal parasties, antibacterial. 

Piperydylpropanone (126), known for many years as isopelletierine, is now referred to as pelletierine, following the suggestion of Gilman and Marion (63). The pelletierine originally described by Tanret was never later isolated or synthesized. 

Two new approaches to the synthesis of deoxynupharidine (14) and its C-l and C-7 epimers were reported. Arata et al. (67) made use of the Mannich reaction of a suitable derivative of isopelletierine and 3-furylaldehyde ( )-7-epideoxy-nupharidine (15) and ( )-l-epideoxynupharidine (8) were proved to be the main products of the reaction. The synthetic route is shown in Scheme 11. Intramolecular Diels-Alder condensation of 1-Azadienes was shown (68) to be a stereoselective route to the total synthesis of (-)-deoxynupharidine (14). The key steps are shown in Scheme 12 from synthon A in four steps alkaloid 14 was obtained. 

The continuing interest in the synthesis of macrocylic alkaloids has been directed this year to the preparation of the cw-quinolizidine group. It is apparent from the work of Hanaoka et al.29 that alkaline conditions for the Mannich condensation of isopelletierine (41) with aryl aldehydes, cf. (39), favour the formation of cis-quinolizidinones. The synthesis of the biphenyl ether alkaloid vertaline (48) was carried out in this way (Vol. 5), and has now been described in full.30... 

Isopelletierine (23) undergoes a Mannich reaction with both m-methoxy- and m-hydroxy-benzaldehyde, to give respectively a mixture of the cis (24 R = Me) and trans (25 R = Me) quinolizidines, and exclusively the tran -quinolizidine (25 R = H). The ratio of stereoisomers in the former reaction varies widely with solvent used. ... 

There is still considerable activity in the synthesis of Lythraceae alkaloids, although no new methods have emerged this year. Details have appeared of two independent syntheses of the biphenyl ether alkaloid decaline. - Arata s approach to the synthesis of decaline (35) cf. Vol. 5) has been applied to lagarine (36), using a benzyl group to protect the phenolic hydroxyl substituent. 4-Arylquinolizid-2-ones, cf. (34), are important synthetic intermediates, and their synthesis from isopelletierine and a variety of 2-bromobenzaldehyde derivatives has been studied. ... 

Hyoscine, hyoscyamine, norhyoscyamine, tigloidine, valtropine, scopolamine, valeroidine, tropine, noratropine, apohyoscine, tropyl butyrate, poroidine, isoporoidine, norhyoscine, acetyltropine, tetramethylputrescine, nicotine, anabasine, isopelletierine... 

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. 

Galinovsky and his co-workers have re-examined the alkaloids of the bark of Punica granatum L. In a sample, labeled pelletierine hydrobromide, that they obtained from Merck (Darmstadt), the only secondary base present was not j3-(2-pelletierine) but isopelletierine identical with a synthetic sample (12). They further found that methylisopelletierine and isopelletierine retain their optical activity in the presence of acid, but racemize in contact with alkali, and the former racemizes appreciably faster than the latter. If the bases were optically active in the plant they would racemize during the process of extraction and isolation unless the work is done rapidly (13). 

The total alkaloid hydrobromide (Merck) and also the crude alkaloid freshly isolated from the bark and worked up by chromatography by the method of Chilton and Partridge (14) yielded no pelletierine (15). The secondary base was isopelletierine, and the dl-hsse picrate melted at 148°, which is very close to the melting point (150°) reported for pelletierine picrate (16). It is concluded that the pelletierine of Tanret and of Hess was isopelletierine. 

Two species of Sedum have been examined for alkaloids, i.e., Sedum acre L. and Sedum sarmentomm Bunge. The first yielded the alkaloids sedamine (83) and sedridine (84, 85), whereas the other contained IV-methyl isopelletierine and its dihydro derivative (86). 

S. sarmentosum contains two liquid alkaloids which are separated by fractional crystallization of the picrates. The least soluble picrate (CigHanOgNi), m.p. 159°, proved to be identical with the picrate of synthetic d(-methylisopelletierine (86). The more soluble picrate (C1BH22O8N4), m.p. 125°, is that of an optically active base C9H19ON, [a] 25.0 (abs. ethanol). On the assumption that this new base was the dihydro derivative of. A -methyl-isopelletierine (.A -methyl-l-(2-piper-idyl)-2-propanol), di-methylisopelletierine was reduced with lithium aluminum hydride and the product converted to the picrate. The two diastereoisomeric forms separated into an oily picrate and a crystalline picrate, m.p. 126° (86). The base recovered from this picrate could not be resolved (93). 

When the methosulfate of l-(2-pyridyl)-2-propanone was hydrogenated the pyridine ring was preferentially reduced to give A-methyl-isopelletierine (130). 

Two syntheses of ( + )-decaline (22a) have been described in preliminary communications (Scheme In one of these, isopelletierine (18), prepared... 

The bark of the pomegranate tree (Punica granatum L.) was first investigated by C. Tanret who isolated from it four alkaloids which he named pelletierine (204), isopelletierine, methylpelletierine, and pseudo-pelletierine (205, 206). Methylpelletierine and pelletierine were observed to be optically active while isopelletierine and pseudopelletierine were inactive. Later, Piccinini (207) found a fifth alkaloid, isomethylpelletierine in the mother liquors obtained from the preparation of pseudopelletierine. Eventually, however, Hess (208) while reinvestigating the bark obtained pseudopelletierine, Piccinini s isomethylpelletierine and a third, optically inactive base, but found no trace of Tanret s optically active methylpelletierine. He could not find any optically active alkaloids and, considering his third base identical with Tanret s isopelletierine (185) renamed the latter base pelletierine. Further, Hess and Eichel (209) considered Tanret s methylpelletierine and Piccinini s isomethylpelletierine as identical but different from methylated pelletierine and named it methyliso-pelletierine (185). 

To these three alkaloids, two more were subsequently added isopelletierine (210) and a-A-methylpelletierine-jS-one (209). The latter was subsequently shown to be methylisopelletierine (188, 211). Altogether, there are therefore four alkaloids present in the bark pelletierine, CsHisON (Tanret s isopelletierine) pseudopelletierine, C9H15ON, isopelletierine. 

Pseudopelletierine is separated by freezing the mixture of crude alkaloids while the bulk of the pelletierine is cr3fstallized as its hydrobromide. The base recovered from the mother liquors is distilled under reduced pressure and the distillate treated with ethyl chloroformate. Repeated fractional distillation of the product affords a first fraction consisting of pure methylisopelletierine and a second fraction, b.p. 150-165°/13 mm. consisting of the urethanes of pelletierine and isopelletierine. Hydrol3fsis of this last fraction resinifies the liberated pelletierine whereas the isopelletierine is recovered and purified by distillation. One hundred kilograms of the bark yields 179 g. of pseudopelletierine, 52.5 g. of pelletierine, 23 g. of methylisopelletierine, and ca. 1.5 g. of isopelletierine. 

---