Dioscorine: Chemistry

Batman is coming… However, this batman is a deadly invasive supervillain capable of smothering an entire ecosystem! Behold the batman yam or Zanzibar yam (Dioscorea sansibarensis). All parts of D. sansibarensis especially the tubers and bulbils are widely implicated as hunting, murder, and suicide poison in parts of Africa where it is native. Today we are going to examine the chemistry of its principal toxin, dioscorine.

Dioscorea sansibarensis

Dioscorine is an alkaloid. Remember that all alkaloids must contain at least one nitrogen atom, and they can be classified according to how the nitrogen atom is incorporated into the alkaloid, usually in the form of a ring. For instance, the tropane alkaloid, which we have discussed previously has a bicyclic structure (ring within a ring). Dioscorine also has a bicyclic ring, but it is called isoquinuclidine (Figure 1). An isoquinuclidine ring is comprised of a hexagonal carbon-nitrogen ring called piperidine, which is incorporated into another piperidine ring. I have highlighted both ring in red and blue under the isoquinuclidine structure in Figure 1, respectively. Repulsion of electrons within the bicyclic ring causes isoquinuclidine to take the shape of a ‘double half-chair’ in 3D space, and the nitrogen atom sticks out from the center of both rings. Look at how chemist numbers isoquinuclidine, carbon-1 starts at the center of both rings, which is connected to the nitrogen atom labelled as number 2. Carbon-5 is where the side component of dioscorine is connected. That is basically a cyclic ester called a lactone. The whole structure of dioscorine is depicted in the right-hand side of Figure 1, and you can see it’s 3D sturcture at the bottom. 

 

Figure 1: Chemical structure of dioscorine.

The isoquinuclidine skeleton of dioscorine is made by Dioscoreaceae plants from another simpler alkaloid called trigonelline, which originates from niacin, or vitamin B3.  Trigonelline is reactive because it contains a permanent positive charge at its nitrogen atom, and the adjacent carbon can be attacked by an electron rich nucleophile to quench this positive charge. Hence, trigonelline can undergo nucleophilic addition with a precursor called an enolate ion, which is derived from an organic acid (beta-keto dicarboxylic acid). This then generates an intermediate product that will produce the isoquinuclidine and ester components of dioscorine. In brief, the intermediate undergoes two intramolecular cyclisation steps, like two snakes biting their own tails to generate the two rings of dioscorine. If you want more challenge, examine Figure 2 carefully, and follow the red, pink, and green arrows to walk yourself through the biosynthesis mechanism of dioscorine. Take note that I've labelled the blueprint numbers for the isoquinuclidine (1–8) and lactone (A–D) fragments, fold it up at the end according to the connected bonds and you'll get dioscorine. 

 

That’s it for today, and in the next post, we will explore the structure activity relationship of dioscorine, and find out why it is so deadly. 

 

Figure 2: Biosynthesis pathway of dioscorine.