Biosynthesis lycopodium alkaloids

The corresponding A -piperideinium cation (41), probably the universal intermediate in piperidine, quinolizidine, and lycopodium alkaloid biosynthesis, is susceptible to nucleophilic attack much like its V-methyl-A -pyrrolinium cation counterpart in pyrrolidine and tropane alkaloid biosynthesis. Moreover, A -piperideine (40) might be reduced to piperidine (42), which now in turn might serve as nucleophilic species. For example, condensation of piperidine (42) with piperoyl-CoA catalyzed by piperidine V-piperoyltransferase (EC 2.3.1.145) yields piperine (43), the main alkaloid found in black pepper where it is responsible for the characteristic pungent taste. 

A third total synthesis of luciduline in its racemic form was reported by Szychowski and MacLean in 1979 [14]. The final aim of the authors was to synthesise an intermediate which may be involved in the biosynthesis not only of luciduline itself but also of other members of the Lycopodium alkaloids family. 

Nyembo et al. [15] proposed in 1978 that the amino acid 34 and other compounds of general structure 35> known as phlegmarines, the stereochemistry of which is not specified, may be intermediates involved in the biosynthesis of Lycopodium alkaloids. 

Two proposals for the biogenesis of the Lycopodium alkaloids were outlined in the previous section. To test these alternative hypotheses a study of the biosynthesis of lycopodine was undertaken. Lycopodine was chosen for experimental study not only because it is the most widely distributed member of this family of alkaloids but also because degradation procedures for the isolation of individual carbon centers or fragments were available from the extensive structural work ). 

In this area the biosynthesis of the Lycopodium alkaloids, e.g. lycopodine (14) and cernuine (15), is of further interest. Lycopodine and cernuine were considered to be modified dimers of pelletierine (16) because two intact molecules of precursors like lysine and A -piperideine were used for the construction of a single molecule of the alkaloids. Paradoxically, however, pelletierine (16) only gives rise... 

Work on the biosynthesis of lycopodine (126) in Lycopodium tristachyum and cernuine (127) ° in L. cernuum, previously published in preliminary form and reviewed,has appeared in full lycopodine and cernuine.It was established that the two alkaloids are derived from two molecules of lysine via a symmetrical intermediate which is in all probability cadaverine. The hypothesis that the Lycopodium alkaloids were modified dimers of pelletierine (125) (Scheme 12) required reappraisal, as pelletierine gave only one each (shown with heavy bonding) of the two CgN units of (126) and (127). 

The biosynthesis of the Lycopodium alkaloids, e.g. lycopodine (5), is still a puzzle. Biosynthesis of these alkaloids from A -piperideine (3) and acetic acid, suggests that these alkaloids are formed by dimerization of a single precursor, for which isopelletierine (4 R = H) is a logical candidate. But, it is quite clear that it is the source for only one half of these molecules. What the precursor for the other half is, remains unknown. 

Gerard RV, MacLean DB (1986) GC/MS examination of four Lycopodium species for alkaloid content. Phytochemistry 25 1143-1150 Hartmann T, Toppel G (1987) Senecionine N-oxide, the primary product of pyrrolizidine alkaloid biosynthesis in root cultures of Senecio vulgaris. Phytochemistry 26 1639-1643... 

The full paper on the biosynthesis of the lycopodium alkaloids from lysine was published.29 xhe possibility that two identical pelletierine units (20). derived from lysine and acetate, would combine to form lycopodlne (21) was not corroborated by double labeling experiments with [4,5-%2 2" "P ll tierine.30 Only the portion of the molecule drawn in heavy line was derived from pelletierine. 

Note to Table 87 As a supplement, other work may be mentioned in which TLC has been a useful, indeed indispensable, help on the animal poisons, taricha- and tetrodotoxine [139b] the lycopodium alkaloid L 9 [10, 49b] anuloline [209b] and the biosynthesis of the calycanthus alkaloid, calicanthine [210b]. 

As a consequence of one additional methylene group present in the side chain of the homolog amino acid L-Lys in comparison with L-Om, the corresponding piperidine, quino-lizidine, indolizidine, and lycopodium alkaloids contain a six-membered piperidine ring instead of a five-membered pyrrolidine ring. Moreover, the fact that both L-Lys and L-Om exhibit a quiet similar chemical reactivity enables L-Lys to undergo similar metabolic conversions as outlined in the previous chapter for the biosynthesis of alkaloids derived from L-Om. 

The first step in the biosynthesis of piperidine, quinoli-zidine, and lycopodium alkaloids is the PLP-assisted decarboxylation of L-Lys to the diamine cadaverine (38) by lysine decarboxylase (EC 4.1.1.18) (Scheme 11.5) [9, 27]. Similar to putrescine, this foul-smelling compound is associated with putrefying animal tissue as one might expect by hearing its name. Next, oxidative deamination of cadaverine by copper amine oxidase (EC 1.4.1.22) yields 5-aminopentanal... 

The biosynthesis of lycopodium, quinohzine, pyridine, or a-pyridone-type alkaloids isolated from Lycopodium species, shares some common steps with the biosynthesis of the previously mentioned piperidine alkaloids [28, 35, 36], The first general intermediate for all lycopodium alkaloids is the piperidine alkaloid pelletierine (45). Again, besides the... 

Huperzine A (1) has undergone clinical trials in China in patients suffering from various memory disorders, including Alzheimer s disease. Significant effects of huperzine A (1) were noted in these patients in terms of their quality of life and it has become available to numerous individuals for the treatment of memory problems. Since the other pharmacological activities of the various types of Lycopodium alkaloids have been poorly studied, this area should also be developed. Similarly, the biosynthesis of Lycopodium alkaloids has been only preliminarily studied, and the pathways have not been characterized with respect to the intermediates and the relevant enzymes. It will further be of value to elucidate the structural and pharmacological features of more Lycopodium alkaloids. 

C16H26N2O, Mr 262.40, mp. 103-104°C, [a]n -20.5° (CH3OH). Alkaloid from some Lycopodiaceae species ( ciubmosses. Lycopodium cernuum and L. carolia-num). It is weakly toxic. The biosynthesis starts from lysine with cadaverine, 1-piperideine, and pelletie-rine as intermediates. ... 

The biosynthesis of the structurally complex alkaloids of the primitive club moss Lycopodium species), e.g. lycopodine 6.43) and cernuine 6.44), has been analysed simply in terms of a pathway which involves the dimerization of two pelletierine units (Scheme 6.11). Substance is given to this hypothesis by the appropriate incorporations of acetate, lysine 6.17), and A -piperideine 6.18) into lycopodine 6.43) and cernuine 6.44). Significantly, these precursors were incorporated equally into both putative pelletierine (CgN) units [27]. 

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