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August 26, 2010
Vinca Alkaloids, And Where They End Up
The Vinca alkaloids are some of the most famous chemotherapy drugs around - vincristine and vinblastine, the two most widely used, are probably shown in every single introduction to natural products chemistry that's been written in the past fifty years. But making them synthetically is a bear, and extracting them from the plant is a low-yielding pain.
A new paper in PNAS shows that there's still a lot that we don't know about these compounds. What has been known for a long time is that they're derived from two precursor alkaloids, vindoline and catharanthine. This new work shows that the plants deliberately keep those two compounds separated from each other, which helps account for the low yield of the final compounds.
As it turns out, if you dip the leaves in chloroform, which dissolves the waxy coating from the surface, you find that basically all the catharanthine is found there. At the same time, even soaking the leaves in chloroform for as long as an hour hardly extracts any vindoline - it's sequestered away inside the cells of the leaves. The enzymes responsible for biosynthesis are probably also in different locations (or cell types), and there are unknown transport mechanisms involved as well. This is the first time anyone's found such a secreted alkaloid mechanism.
Why does Vinca go to all the trouble? For one thing, catharanthine is a defense against insect pests, and it also seems to inhibit attack by fungal spores. And what the vindoline is doing, I'm not sure - but the plant probably has a good reason to keep it away from the cantharanthine, because producing too much vincristine, vinblastine, etc. would probably kill off its dividing cells, the same way it works in chemotherapy.
The authors suggest that people should start looking around to see if other plants have similar secretion mechanisms. And this makes me wonder if this could be a way to harvest natural products - do the plants survive after having their leaves dipped in solvent? If they do, do they then re-secrete more natural waxes to catch up? I'm imagining a line of plants, growing in pots on some sort of conveyor line, flipping upside down for a quick wash-and-shake through a trough of chloroform, and heading back into the greenhouse. . .but then, I have a vivid imagination. . .
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