Is Natural Product Synthesis Interesting?

This is a slightly provocative post – I would welcome comments.
When the Nobel prizes were announced this year there was consternation in some of the chemical blogosphere that the chemistry prize had gone to a biologist (see links in my earlier post). But others argued that chemists had lost the plot and that biology is now where the action is. It was important not just to do research in one's own community but to appeal to a wider audience.
A lot of chemistry (reflected by the chemical blogosphere) is concerned with making compounds. A subset of this is the synthesis of natural products, compounds produced by organisms (fungi, bacteria, plants, marine invertebrates, etc.). These compounds often have biological activities (e.g. to kill other other organisms) and are frequently useful in medicine. Typical examples are taxol (anticancer, from the Pacific yew tree) , ciclosporin (immunosuppressant from a fungus) and vancomycin (antibacterial from bacteria). They are in widespread clinical use and this is reflected by a very large literature. I have used Pubmed to get a base metric – I simply enter the name and see how many references there are and the earliest date:

• taxol (1971) 12505 references
• vancomycin (1955) 12225 references
• ciclosporin (1980) 20505 references

(The numbers are approximate as names can vary – we also find "cyclosporin" – but Pubmed with its MeSH terminology is very good about synonyms).
These compounds are difficult and expensive to extract from natural sources so there is clear value in trying to make them more cheaply by synthetic chemistry. Moreover it may be possible to synthesize similar compounds which are better or much easier to make or both. So not surprisingly the pharmaceutical industry (in which I have worked) and academia are interested in synthesizing complex molecules. And this is reflected, for example, in TotallySynthetic's excellent blog where he reviews the syntheses of natural products.
But are the targets chosen because they are useful, or because they are difficult? And do the results of such synthesis find their way into the clinic or use as biological tools? To be fair, it's important to remember that it takes a long time to develop drugs, and also that chemical synthesis might be a prerequisite step before any other science can be done. Bearing that in mind, here are the Pubchem metrics for the compounds in the last 2 months of Totally Synthetic's blog (back to 2006-09-01). The table shows:

• the name used in the blog. (Sometimes there are additional letters which I have removed to increase the hits). Bear in mind that some compounds might have synonyms, but Pubmed is pretty good about this.
• The date of the first abstract in Pubmed. This is often the first report of the isolation of the compound and its possible biological activity.
• The number of papers in chemistry journals. These are mostly reporting the synthesis, but some might discuss the elucidation of structure. The latest chemistry paper as abstracted by Totally Synthetic is sometimes not yet included in Pubmed, but in general all the major chemistry journals are reviewed.
• The number of papers in "non-chemistry" journals. This is subjective but these are the ones where biosynthesis, biological activity, medicinal properties, etc. are likely to be reported.

Out of 22 compounds a few have a significant biological literature. Many, even when reported some time back have none. So it is difficult to argue that they are synthesised because they are interesting.
There are other reasons than interesting biology for doing this type of synthetic chemistry. It can lead to new synthetic methodology which could be of use to the chemical industry in general. And it may be good training for the chemistry-specific part of a PhD. So I welcome comments – they will all be posted.