Akuammicine

The alkaloid akuammicine 1 is known to decompose slowly when heated in methanol. In a careful study of this reaction it was found that when 1 was heated with methanol at 100°C in a sealed tube for 3 hours it had decomposed to the extent of 80%, and the betaine 2 was isolated in 70% yield. Under the same conditions, but at a temperature of 140°C, decomposition was complete within 2 hours, and the two products which were isolated were 3-ethylpyridine (48%) and 3-hydroxycarbazole 3 (60%). 

Favorskii-type reactions, which are known to be sensitive to the base and solvent used and to the nature of the halogen leaving group, continue to attract attention, and in combination with other bond forming processes can often be manipulated to provide useful synthetic methods. For example, the chloroketone 1 gives pivalic acid on treatment with 40% aqueous NaOH, but only 3-hydroxy-3-methyl-2-butanone on reaction with either 20% aqueous Na2CC 3 or 14% aqueous or ethanolic KOH. When a mixture of 1 (3.5 eq.) and benzaldehyde (1 eq.) was treated with 14% ethanolic KOH (7 eq.) at room temperature for 3 hours, however, the lactone 2 was the major 

Zinc dust distillation of the indole base A (X) gives comparatively high yields of 3-ethyl-2-methylindole and 3-ethylpyridine. Thus, it is possible to account for all the carbon atoms of X, and the structure of the latter is confirmed, with the exception of the point of attachment of the asterisked carbon atom (C-16) to the piperidine ring (32). 

There remains for discussion the very interesting decomposition 

At 140° in methanol, a much more extensive decomposition of akuammicine occurs, and the products isolated are 3-ethylpyridine and 2-hydroxycarbazole (XXXV). The formation of 3-ethylpyridine is presumably the result of a normal Hofmann degradation of the pyri-dinium ester corresponding to XXXIII the other product should consequently have been methyl 3-vinyl-2-indolylacetate (XXXIV), but this was not obtained. It was accordingly suggested that the 2-hydroxycarbazole obtained was formed from XXXIV by intramolecular nucleophilic attack of the vinylogous enamine methylene group on the carbomethoxy group (arrows in XXXIV), followed by elimination of methanol and aromatization (39). 

Pseudoakuammicine, C20H22N2O2, mp 187°, pK 7.47, was first isolated from Picralima seeds by Henry (5), who reported its rotation as [ ]d —83°. Robinson and Thomas (30) noted that its IR- and UV- 

In more recent investigations, Edwards and Smith (40) have carried out further extractions of Picralima seeds, and have found pseudoakuammicine to be optically inactive its 2,16- and 19,20-dihydro derivatives are also optically inactive. Pseudoakuammicine and its two dihydro derivatives have IR-spectra identical with those of the corresponding derivatives of akuammicine hence, pseudoakuammicine is (+)-akuammicine. This conclusion was confirmed by resolution of pseudoakuammicine by fractional crystallization of the (+ )-tartrate. The more soluble salt gave akuammicine, and the less soluble salt gave (+ )-akuammicine, mp 181°-182.5°, [a]f,3° +720° (MeOH). On being mixed with an equimolecular proportion of akuammicine, (+ )-akuam-micine gave pseudoakuammicine. 

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Rosenmund group never applied this reaction to the Strychnos alkaloids (e.g., akuammicine, 58) is somewhat surprising. 

Scott and co-workers have also reported on the isolation of alkaloids from C. roseus cell suspension cultures 126). The cell line used, identified as CRW, afforded akuammicine (49), catharanthine (4), and strictosi-dine (33), and feeding experiments with labeled tryptophan led to incorporation into ajmalicine (39), akuammicine (49), catharanthine (4), and vindoline (3). The ability to produce alkaloids was carried through 8 successive generations. 

Deacetylakuammiline (64) 10-Hydroxy-deacetylakuammiline (68) Pleiocarpamine (55) Akuammicine (49) Xylosyloxyakuammicine Dihydrocondylcarpine Vinervine Tabersonine (38) + ... 

Akuammicine Catharanthus roseus Catharanthus ovalis Rhazya stricta... 

Akuammicine 81, 82, 200 Akuammidine 16 Albertidine 103 Albine 34, 100 Alcuronium 38 Alginate 203 Alioline 16, 38 AUcaloid-C 150 Allocryptopine 22 Aloe-emodin 35, 45 Aloperine 103 Alstomacroline 16, 37 Alstomacrophyline 37 Alstonerine 16, 37 Alstophyline 37 Alstoumerine 16, 37 Amabiline 52... 

Alkaloids like preakuammicine (Figure 6.79) and akuammicine (Figure 6.75) contain the C10 and C9 Corynanthe type terpenoid units respectively. They are, however, representatives of a subgroup of Corynanthe alkaloids termed the Strychnos type because of their structural similarity to many of the alkaloids found in Strychnos... 

Strychnine-Akuammicine-Ellipticine Group. 11-Methoxyicajine (110)77 and 15-hydroxystrychnine,78 a new alkaloid, have been isolated from Strychnos nux-vomica seeds, and 11-methoxydiaboline from S. rubiginosa.58 10-Hydroxy-akuammicine (sewarine) occurs in the leaves of Rauwolfia volkensii,60 and 11-methoxyakuammicine in Alstonia odontophora.59... 

Haldina cordifolia Ridsd.) (bark) Alstonia scholaris R.Br. (root bark, stem Apocynaceae Akuammicine (81,82)... 

From the roots of Rauwolfia cambodiana, the alkaloids pelirine and ajmaline have been isolated (73). The alkaloids akuammicine, akuammi-cine Nb-oxide, akuammicine Nb-methiodide, pseudoakuammigine, and tubotaiwine have been newly recorded from the root bark of Alstonia scholaris R.Br. (Apocynaceae) echitamine is isolated as the major alkaloid, along with Nb-demethylechitamine, as well as three unidentified echitamidine isomers, and other known alkaloids. The stems of the same plant yielded echitamine, Nb-demethylechitamine, tubotaiwine, pricri-nine, and other unidentified echitamidine isomers (81,82). Apart from the alkaloids in the heteroyohimbine group from roots of Rauwolfia serpentina, a new base, named ajmalimine (73) (53), and ajmalinimine (74)... 

The root bark of S. variabilis De Wild., from Zaire, contains two alkaloids, identified as (-)-2/3,16 8-dihydro-akuammicinol and (+)-Na-acetyl-2j8,16a-dihydro-akuammicinal a third alkaloid, probably dimeric, was also isolated, but in too small an amount to allow elucidation of its structure.105... 

Strychnine-Akuammicine-Ellipticine Group. A new alkaloid encountered in the culture of cell line 943 of Catharanthus roseus has been formulated, on the basis of its n.m.r. and mass spectra, as the /S-xyloside (147) of 9- (or 12-)hydroxy-akuammicine.42a Akuammicine and 10-methoxyakuammicine are reported to be present in the leaves of Rauwolfia oreogiton.43a Diaboline has been found in the root bark of Strychnos jobertiana Baill., and 11-methoxydiaboline in the root bark of S. 

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