Plant-derived artifacts

The first extractions performed on different parts of the yew (leaves, bark, roots, or wood) employed the usual techniques for the isolation of alkaloids 1% sulfuric acid applied directly to the leaves or after their extraction with methanol (12). This rather rough treatment did not allow isolation of the very labile substances present in this plant. However, the use of petroleum ether for the wood (13) and alcohol for the trunk bark (2) or leaves (14) led to the isolation of several interesting products such as the baccatin derivatives. These observations explain why a certain number of taxanes have been identified only by way of their derivatives, artifacts of the extraction process. 

Most all of the organic compounds which have been reported from studies of cotton plant parts and cotton trash have been included in this review. Only those which seem most unlikely to be cotton-derived natural products have been excluded. For example, the phthallates reported as "air space volatiles of the cotton plant" are likely artifacts derived from cjommon plastics (.9) some hydrocarbons found to be in cotton lint and waste probably came from a source obtained from petrolexim W and aflatoxln is presumably a mold metabolite (36). A few other compounds have been excluded for similar reasons. 

Until the mid 1960 s the only plant cannabinoid whose structure was fully elucidated was cannabinol (CBN) — a constituent which actually may represent an oxidation artifact. However, on the basis of CBN, the main cannabinoid structure skeleton became known. Thus, cannabidiol (CBD), which had been independently isolated in pure form by Adams and by Todd, was correctly assumed to be, like CBN, a terpenoid derivative attached to olivetol. But its exact structure was not elucidated. The psychoactive components of cannabis were assumed to be related tricyclic derivatives. On the basis of the tentatively elucidated constituents, Todd suggested that the cannabinoids may be formed initially in the plant by condensation of a menthatriene with olivetol. 

The advances in isolation methods made possible a clarification of the chemistry of cannabis. In 1963, our group reisolated CBD and reported its correct structure and stereochemistry. A year later we finally succeeded in isolating pure A -tetrahydrocannabinol (A -THC), elucidated its structure, obtained a crystalline derivative and achieved a partial synthesis from CBD. Several years later, a minor psychotomimetically active constituent, A -THC, was isolated from marijuana. Whether this THC isomer is a natural compound, or an artifact formed during the drying of the plant, remains an open problem. 

Little is known of the biological and chemical behavior of the fluorodichloromethyl derivatives. Rio-tolysis of dichlofluanid results in the formation of N,N-dimethyl-N -phenylsulphamide, phenyl isocyanate and isothiocyanates and dimethylamidosulfonyl chloride GC-MS analysis also indicates the presence of bis-(fluorodichloromethyl) disulfide and two ketones, the latter being artifacts arising from the solvent, acetone. Dichlofluanid metabolism in plants yields N,N-dimethyl-N -phenylsulphamide (1 6), but nothing is... 

A Papua New Guinea sponge, Pseudoceratina sp., contains the unusual alkaloids ceratamines A (1142) and B (1143), and a biogenesis involving histidine and tyrosine is proposed (1173). The fermentation broth from Aspergillus fischeri var. thermomutatus has yielded CJ-12662 (1144) and UK-88051 (1145) (1174). The former metabolite was confirmed by X-ray spectroscopy and partial synthesis. A marine-derived Streptomyces sp. produces the novel pyrrolizidine 5-chlorobohem-amine C (1146), which was shown not to be an isolation artifact (1175). The Chinese medicinal plant Huperzia serrata has furnished 2-chlorohyperzine E (1147) (1176). 

The occurrence of reserpine has been reported from all Rauwolfia species, with the exception of about half a dozen in which it is probably present in minute amounts. Renoxidine, the A-oxide of reserpine, has been isolated from R. vomitoria, R. serpentina, and R. canescens, and it may not be a natural product, since it could have been derived by autoxi-dation of the tertiary base which is abundant in these plants. If it was an artifact, the occurrence of other analogous A-oxides should have been noted, but so far the only other recognized case is raujemidine A-oxide, which is found along with the parent alkaloid, raujemidine (a minor base of R. canescens). In contrast to reserpine, deserpidine and rescinnamine are of restricted distribution, each being recognized so far in about ten species only. 

During the isolation of cathinone, 3,6-dimethyl-2,5-diphenyl pyrazine (3) was also found (14). This is doubtless an artifact, the product of oxidative dimerization of cathinone which involves the formation of condensation product 4 as an intermediate (18). Also found was the diketone (5) and the cinnamoyl compound (6) (14), later shown to have the (S) stereochemistry illustrated and named merucathinone (6,19,20). Merucathine (7) has also been isolated (6,21,22), and this and merucathinone are minor components. (-)-Norephedrine (8) also occurs in khat (14), and its iV-formyl derivative (9) has been found in plant material of South Arabian origin (23). Despite earlier positive reports, ephedrine and pseudoephedrine have not been verified as components of khat (14). HPLC has been employed to separate and quantify mixtures of the khatamines cathinone, (+)-norpseudoephedrine, and (—)-norephedrine in connection with a study of their distribution in different parts of the khat plant and in specimens of different geographical origin (20,21). 

Epoxy -16 - hydroxy -16 - methoxycarbony 1 - 3 - oxo -1,2- didehydro-aspidospermidine (127) has been extracted from the seeds of Amsonia elliptica (101). However, this is almost certainly an artifact, derived by aerial oxidation of 3-oxotabersonine (107), which occurs in the same plant, or its epoxide. 

Noteworthy results in the phytochemical studies, the N-oxides of several Amaryllidaceae alkaloids have been found for the first time in Amaryllidaceae plants, accompanied by the corresponding free bases (52) ungiminor-ine A-oxide (10) (from Pancratium maritimum), and O-methyllycorenine A-oxide (329) and homolycorine A-oxide (330) (from Lapiedra maritinezii). The stereochemistry of their nitrogen atoms was deduced based on 2D NOESY experiments. Furthermore, it has been established that these A-oxide derivatives are genuine natural products, and not artifacts, by the demonstration that the free bases are not converted into A-oxides when subjected to the same extraction procedure. It is noteworthy that the A-oxides have been isolated accompanied by the corresponding free bases. 

Ismine (424) and three new phenanthridine derivatives, N-methylcrinasi-dine (425), 8,9-methylenedioxyphenanthridine (426) and N-methyl-8,9-methylenedioxyphenanthridinium chloride (427), were found in the leaves and bulbs of Lapiedra martinezii (53). The co-occurrence of ismine (424) in the plant gives an indication of the biosynthetic relationship between the four alkaloids (55). The three alkaloids isolated are not artifacts since... 

A reexamination of the aerial parts of Orixa japonica resulted in the isolation of a new ketone, orixinone (72), which was present in the stems only (59). The structure of orixinone was established by spectroscopy and by its formation from the diol ( )-orixine (73) by means of dehydration with aqueous acid. The probability that the isoprenoid diol evoxine is formed from the epoxide alkaloid 174 (see Section IV,A,3) during isolation suggested that orixine, obtained from the root bark of O. japonica, and orixinone might be artifacts derived from epoxide 106 (see Section III,E,1). The availability of the synthetic epoxide prompted a thin-layer chromatographic study of the constituents of the leaves and stems of the plant, but neither the epoxide nor the orixine was detected. 

A base isolated from Euchresta japonica by extraction with methanol was shown by spectroscopic studies and by its synthesis from (-)-cystisine and methyl bromoacetate to be methyl 12-cytisine acetate (4). This compound is apparently an artifact derived from the new alkaloid (5) extraction of the plant with aqueous ethanol gave the latter compound as its zwitterion, and the methyl ester (4) was not detected. "... 

The fresh bark of Rhamnus frangula and most Cassia species contains anthrones and not anthraquinones (Leistner, 1985). After storage and extraction, anthraquinones and di-anthrones are isolated but are probably artifacts. Except for a dubious record of acetate-derived anthraquinones in the Scrophulariaceae, these compounds are not yet recorded from orders of plants that produce iridoid monoterpenes (see Chapter 20). 

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