Lysinederived alkaloids

L-lysine furnishes alkaloids with at least four different nuclei. It is a protein amino acid, one of the most important alkaloid precursors. L-lysine-derived alkaloids have a basic skeleton with C5N (the piperidine nucleus) and C5N +____

(indolizidine, quinolizidine and pyridon nuclei).

2.6.1. Pelletierine, lobelanine and piperine synthesis pathway

Alkaloids with the piperidine nucleus, such as pelletierine (Punica grana-tum), lobelanine (Lobelia inflata) and piperine (Piper nigrum), have a typical biosynthesis pathway. It starts with L-lysine and continues via cadaverine (bio-genic amine), A1-piperideine and A^piperidinium cations and lobelanine, to be synthesized as lobeline. Piperine is synthesized from A1 -piperideine via piperidine (Figure 49). For the transformation from A1-piperideine to A1-piperideine cation, the residue from acetyl-CoA is needed, together with SAM activity in the transformation to lobelanine. Piperine is synthesized from piperidine through the formation of amide.

Figure 49. Diagram of the pelletierine, lobelanine and piperine synthesis pathway.

Alkaloids Images



2.6.2. The swansonine and castanospermine synthesis pathway

Swansonine and castanospermine synthesis starts with the a-aminoacid, y-semialadehyde and, via piperidine-6-carboxylic acid synthetases, L-pipecolic acid. This compound is a substrate to HSCoA and acetyl-CoA. As a result of this activity, the second ring is established. Subsequently, it changes to 1-indolizidinone and, by oxidation reaction, produces castanospermine or swansonine (Figure 50).

Both castanospermine and swansonine occur in some legume plants, such as Castanospermum australe and Swainsona canescens respectively. They are hybrid molecules compounded of pyrrolizidine and quinolizidine alkaloids, and have shown some resistance to the AIDS virus. Certainly, the above-mentioned alkaloids are also toxic for animals.

2.6.3. The lupinine, lupanine, sparteine and cytisine synthesis pathway

L-lysine is a very important precursor for alkaloids with the quinolizidine nucleus. This group of alkaloids can be divided according to their construction into three sub-groups as follows: bicyclic alkaloids (1st sub-group), tricyclic (2nd sub-group) and tetracyclic alkaloids (3rd sub-group)7. In the older studies, a division of quinolizidine alkaloids was established according to alkaloid type. Kinghorn and Balandrin215 divided these alkaloids into (1) quinolizidines with simple substituents, (2) the leontidine-type, (3) the sparteine/lupanine-type, (4) the esters of sparteine/lupanine-type, (5) the tricyclic degradation products of sparteine/lupanine-type, (6) the pyridine bases-type, (7) the matrine-type, (8) the Ormosia-type and (9) quinolizidine alkaloids having miscellaneous structures.

Figure 50. Diagram of the swansonine and castanospermine synthesis pathway.

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 synthesis32'216'217'218'219'220, there are different experimental variants of this conversion. According to new experimental data32, 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 molecules216'217'219'220. In the cadaverine conversion, the participation of diamine oxidase is more reliable than the oxosparteine synthase mentioned by some older studies219'220.

Schiff base Aldol-type re^bn

Hydrolysis of imine to amine Oxidative deamination

Schiff base Aldol-type re^bn

Hydrolysis of imine to amine Oxidative deamination

Schiff base

Schiff base

Lupinine From Lysine
Figure 51. Diagram of the lupinine, sparteine, lupanine and cytisine synthesis pathway. Abbreviations: PLP = coenzyme pyridoxal phosphate; C = cleavage of C4 unit.

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