Indolizidine Alkaloids

2.4.3 Indolizidine Alkaloids


The indolizidine alkaloids are usually characterized by the presence of a 5-membered and a 6-membered cyclic ring with a N-atom fused in them as shown below:

indolizidine alkaloids
The two typical examples of indolizidine alkaloids are, namely: castanospermine and swansonine, which shall be discussed hereunder:

A. Castanospermine

Biological Source It is obtained from the seeds of the Australian leguminous tree Castanospermum australe A. Cunn. (Leguminosae) (Moreton Bay Chestnut).
Chemical Structure

Castanospermine
[1S-(1α, 6β, 7α, 8β, 8aβ]-Octahydro-1, 6, 7, 8-indolizinetetrol; (C8H15NO4). It is a polyhydroxy alkaloid.
Isolation The isolation of the naturally occurring (+)-form of castanospermine from the seeds of the Australian leguminous tree has been duly accomplished.*
Characteristic Features
1. The crystals obtained from aqueous ethanol have mp 212-215°C (decomposed).
2. Its specific optical rotation is [α]D25  +79.7o (C = 0.93 in water); and dissociation constant pK 6.09.
Uses Its has demonstrated activity against the AIDS virus HIV, by virtue of their ability to inhibit glyosidase enzymes involved in glycoprotein biosynthesis. However, the glycoprotein coating seems to be vital for the proliferation of the AIDS virus.

B. Swainsonine

Biological Source It is obtained from the plant Swainsona canescens (Leguminosae/Fabaceae).
Chemical Structure

Castanospermine
[IS-(1α, 6β, 7α, 8β, 8aβ)-Octahydro-1, 2, 8-indolizinetriol; (C8H15NO3).
Biosynthesis of Castanospermine and Swainsonine These two alkaloids are regarded as a hybrid between the pyrrolizidine and quinolizidine alkaloids. It is, however, pertinent to mention here that these two alkaloids though are derived from lysine, yet their origin entirely deviates from the usual and common lysine-derived moieties in that L-pipecolic acid is found to be an intermediate in the pathway. In fact, there are two established routes known to the formation of pipecolic acid in nature, as shown below; wherein the point of difference solely based on whether the N-atom is taken-up either from the α- or the €-amino portion of lysine.
In short, for the indolizidine-alkaloid biosynthesis the following salient features may be observed, namely:
Pipecolic acid is produced via the aldehyde and Schiff base by retaining the N-atom from the aamino function,
* Indolizidine nucleus is formed subsequently by incorporating a C2-acetate unit through simple reactions,
* The resulting compound leads to the formation of castanospermine through a sequential hydroxylation reactions,
* Also a branch point compound results into the formation of swainsonine that essentially possess the opposite configuration at the ring fusion.

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