Alkaloids oxygenation

Since the late 1960s, several carbazole alkaloids oxygenated in the 3-position were isolated from diverse natural sources, the majority of which were isolated from different plant sources. However, in 1979, Moore et al. reported the isolation of two unusual, non-basic, 3-oxygenated carbazole alkaloids, hyellazole (245) and chloro-hyellazole (246), from the blue-green marine algae Hyella caespitosa (225). These alkaloids have structures entirely different from those of the carbazole alkaloids isolated from terrestrial plants. 

A number of alkaloids oxygenated at C-6 of the crinane skeleton have been isolated, including 6-hydroxycrinine (362) (24), 6-hydroxybuphanisine (363) (24), papyramine (390) (65,177), 3-epipapyramine (391) (60), and 6-methoxy-crinamine (380) (44). As judged by examination of the H-NMR spectra, the two epimeric diastereomers of each of the 6-hydroxylated alkaloids 362, 363, 390, and 391 were in equilibrium, but 380 appeared to be stereochemically homogeneous although the relative stereochemistry was not established. The structures of these compounds were deduced principally from a combination of NMR and mass spectral studies and comparisons with known alkaloids. 

It is interesting to note that the occurrence of C-7 oxygenated aporphine alkaloids with the C-6a R configuration is limited to the families Annonaceae, Lauraceae, Magnoliaceae, and Menispermaceae. Aporphine alkaloids oxygenated at both C-4 and C-7 have been found in the Annonaceae, but (-)-stephadiolamine /3-A-oxide (48) is the first known alkaloid hydroxyl-ated at both C-4 and C-7 and having a cis relationship between H-6a and H-7. (-)-O-Acetylsukhodianine is the first known example of a naturally occurring 7-acetoxylated aporphine (30). 

Part 3. Aspidospermine-type alkaloids oxygenated at C-3 and their derivatives... 

Dictamnine (7, R = Me) was a specific precursor of skimmianine (7, R = Me, 7,8-diOMe) and other furoquinoline alkaloids oxygenate in the aromatic ring in Skimmia japonica and Choisya ternate [41] similar results were obtained with cell cultures of Ruta graveolens [104]. Dihydro- (5) and furoquinolin-4-ones (8) are also known. 

Carbon-oxygen bonds are formed by the Ullmann reaction (- coupling of aryl halides with copper) which has been varied in alkaloid chemistry to produce diaryl ethers instead of biaryls. This is achieved by the use of CuO in basic media (T. Kametani, 1969 R.W. Dos-kotch, 1971). 

Among the examples of monoindole bases being discussed, vincamine (109) is the principal alkaloid of Vinca minorC. and has received some notoriety because it apparently causes some improvement in the abiUties of sufferers of cerebral arteriosclerosis (78). It is beheved that this is the result of increasing cerebral blood flow with the accompanying increase in oxygenation of tissue as a result of its action as a vasodilator. 

Conhydrine, CgHj, ON. This oxygenated alkaloid was isolated by Wertheim. It crystallises in colourless leaflets, has a coniine-like odour, can be sublimed and is strongly basic, m.p. 121°, b.p. 226°, Wd 4" 10°- It is soluble in alcohol or chloroform, moderately so in water and in ether, from which it crystallises readily. The salts are crystalline the aurichloride small rhombs or pri.sims, m.p. 133° the benzoyl derivative m.p. 132°. 

Constitution. Pelletierine behaves as a secondary amine and the oxygen atom of the alkaloid is present in the form of an aldehyde group, since the base yields an oxime, convertible by the action of phosphorus pentachloride into a nitrile, b.p. 104-6°/13 mm., which is hydrolysed by caustic potash in alcohol to an acid, the ethyl ester of which is Loffler and Kaim s ethyl -2-piperidylpropionate. Pelletierine is not directly oxidisable to this acid. It also yields a liquid hydrazone, b.p. 130°/20 ram., which with sodium in alcohol at 136-70° reduces to dZ-eoniine. These reactions are explained by the following formulas, in which pelletierine is represented as -2-piperidylpropionaldehyde. 

Codeine is therefore a methyl ether of morphine, whilst thebaine is a methyl ether of an enolic form of codeinone. There has been much discussion as to the function of the third or indifferent oxygen in the three alkaloids, and its nature has only been disclosed by a study of degradation products. 

Constitution of Harmine and Harmaline. Harmaline is a dihydro-harmine. Both bases on reduction yield tetrahydroharmine and in both the single oxygen atom is present as methoxyl. Knowledge of the constitution of the two alkaloids is mainly due to the work of O. Fischer and his colleagues, and more recently to the researches of Perkin and Robinson. 

Delphinine contains one hydroxyl, one methylimino and four methoxyl groups, which with the acetoxy and benzoyloxy groups accounts for all the oxygen atoms of the alkaloid. 

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