Quinolizidine alkaloids pathways

The synthesis pathway of quinolizidine alkaloids is based on lysine conversion by enzymatic activity to cadaverine in exactly the same way as in the case of piperidine alkaloids. Certainly, in the relatively rich literature which attempts to explain quinolizidine alkaloid synthesis °, there are different experimental variants of this conversion. According to new experimental data, the conversion is achieved by coenzyme PLP (pyridoxal phosphate) activity, when the lysine is CO2 reduced. From cadeverine, via the activity of the diamine oxidase, Schiff base formation and four minor reactions (Aldol-type reaction, hydrolysis of imine to aldehyde/amine, oxidative reaction and again Schiff base formation), the pathway is divided into two directions. The subway synthesizes (—)-lupinine by two reductive steps, and the main synthesis stream goes via the Schiff base formation and coupling to the compound substrate, from which again the synthetic pathway divides to form (+)-lupanine synthesis and (—)-sparteine synthesis. From (—)-sparteine, the route by conversion to (+)-cytisine synthesis is open (Figure 51). Cytisine is an alkaloid with the pyridone nucleus. 

This pathway clearly proves that the first quinolizidine alkaloid to be synthesized is (—) lupinine (two cycling alkaloids) and subsequently both (+)-lupanine and (-)-sparteine. This is a new approach to the synthesis of this type of alkaloids because in the older literature just four cycling alkaloids (lupanine and sparteine) were mentioned as the first synthesized molecules . In the cadaverine conversion, the participation of diamine oxidase is more reliable than the oxosparteine synthase mentioned by some older studies °. 

This group of alkaloids has a pyridone nucleus and generally takes the tetracyclic or tricyclic form. The a for pyridone alkaloids is L-lysine, while the j8, q> and X the same as for other quinolizidine alkaloids. Quinolizidine alkaloids containing the pyridone nucleus are the P from the (—/-sparteine by cleavage of the C4 unit. The first quinolizidine alkaloid with the pyridone nucleus is tricyclic cytisine, which converts to four cyclic alkaloids. In this synthesis the anagyrine, the most poisonous quinolizidine alkaloid with a pyridone nucleus, has its own synthesis pathway. 

Unique subcellular compartmentation is also present in quinolizidine alkaloid biosynthesis, which occurs in the mesophyll chloroplasts of some legumes.158 One of the enzymes catalyzing the last two acylations of the pathway in Lupinus albus occurs in the cytoplasm, whereas the other resides in the mitochondria/59 Although the quinolizidine nucleus appears to be synthesized in the chloroplast, subsequent modifications can occur only after alkaloid intermediates are transported to the cytosol and mitochondia. Quinolizidine alkaloids appear to accumulate in vacuoles of epidermal cells where their defensive properties are most effective. 

Quinolizidine alkaloids a group of alkaloids containing the quinolizidine (norlupinane) ring system. The most important Q.a. are the Lupin alkaloids (see), which are synthesized from lysine via cadaver-ine. The Nuphara alkaloids (see), in contrast, also possess a Q.a. ring system, but are synthesized by the terpene pathway. 

In general, alkaloids derive from the metabohsm of amino acids such as phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp), omitine (Om), or lysine (Lys). Quinolizidine alkaloids derived from L-lysine. Its decarboxylation by means of the enzyme lysine decarboxylase gives cadaverine (Cad), the first detectable intermediate of this biosynthetic pathway (Scheme 14.1). 

In Figure 1.2, quinolizidine alkaloids found in completely unrelated taxonomic units are shown. All quinolizidine alkaloids have the same basic ring structure, but the compounds are formed by different biosynthetic pathways. There is no reason to suppose that a certain well-defined chemical compound found in two unrelated species is necessarily formed in both by the same pathway. Kasprzykowna (1957), for example, writes, One... 

The mass spectra of deuterated C30 alkaloids, obtained as a result of reduction of hemiaminals with NaBD4, confirmed the fragmentation pathway leading to the mlz 178 ion (72). As shown in Scheme 16, deuteration at C-6 results in an increase of the mlz 178 ion by one mass unit. On the other hand, deuteration at C-6 does not increase the mass of the ion. In spectra of dideuterated compounds an mlz 179 ion appears, i.e., increased by one mass unit. On the basis of the above data it was concluded that the characteristic fragment (mlz 178 ion) of the C alkaloids derives from the AB quinolizidine ring. 

An efficient new methodological pathway for the preparation of the polyhydroxylated alkaloids, indolizidines, and quinolizidines was developed through (4a) catalyzed RCM/allylic amination or, alternatively, RCM/haloamination strategies (equations), starting from a methyl ftiranoside precursor ... 

Sites of biosynthesis are compartmentalized in the plant cell. While most biosynthetic pathways proceed (as least partially) in the cytoplasm, there is evidence that some alkaloids (such as coniine, quinolizidines and caffeine), furanocoumarins and some terpenes (such as monoterpenes, diterpenes. 

The most common group of alkaloids possessing a quinolizidine nucleus is that of the lupine alkaloids which can simply be classified as bicyclic (lupinine/epilupinine type), tricyclic (cytisine type) or tetracyclic, (sparteine/lupanine or matrine type). Fig. (23). This grouping is made according to structure complexity and without considering biosynthesis, as the detailed biosynthetic pathways are still not completely understood. 

The conversion of lupanine into camoensidine may represent a biosynthetic pathway, and cleavage of the C-16 C-17 bond of a tetracyclic quinolizidine [cf. mamanine (3)] followed by carbon-carbon cyclization could lead to tetracyclic derivatives containing terminal piperidine rings. New alkaloids of this type have been obtained recently. Aloperine was first isolated from Sophora alopercuroides over forty years ago, and structure (12) has now been assigned to the alkaloid on the basis of spectral studies. Allylaloperine (13) is a constituent of the same species. Nitraramine (14) and 7V-hydroxynitraramine (15) from Nitraria schoberi are... 

Lythraceae Alkaloids.—Cryogenine (18) has been shown to incorporate [3- " C]-phenylalanine in Heimia salicifolia. Oxidative degradation established the incorporation of labels at the positions shown in (18) the difference in incorporation of the two units may be a function of the stage at which they normally enter the biosynthetic pathway. Although ring d and the whole of its C3 side chain are probably derived from phenylalanine, it is not yet clear whether this precursor supplies three or only one carbon atom of the quinolizidine system. 

Pyrrolizidine, quinolizidine, and indolizidine alkaloids are chemically diverse and restricted in distribution. Some similarities in structures and biosynthesis exist, but as the pathways become more clear, these three major groups of alka-... 

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