Tamiflu from star anise; optical isomerism and me; bacteria resistant to antibacterial soap and ALL

[eub]

The Wikipedia article on oseltamivir (Tamiflu) says that the world production of oseltamivir is limited by the supply of star anise:

the major bottleneck in oseltamivir production is the availability of shikimic acid, which cannot be economically synthesized and is only effectively isolated from Chinese star anise; although most autotrophic organisms produce shikimic acid, the isolation yield is low. A shortage of star anise is one of the key reasons why there is a worldwide shortage of Tamiflu (as at 2005). Star anise is grown in four provinces in China and harvested between March and May. The shikimic acid is extracted from the seeds in a ten-stage manufacturing process. 90% of the harvest is already used by Roche in making Tamiflu.

Me, I have been editing the Wikipedia article on optical isomerism, which is all well and good except that I am thinking the entire complex of stereochemistry-related articles needs to be refactored. Wikipedia's system -- for history tracking, and for discussion -- is really all built around editing of individual pages.

A 2001 CDC conference paper with some interesting detail on how triclosan works and how bacteria develop resistance to it. Apparently antibacterial soap selects not just for triclosan resistance but for UBERBACTERIA.

MarA is a component of a multiple antibiotic resistance locus, marRAB. When marA is activated, the cell becomes resistant to antibiotics, oxidative stress agents, organic solvents, and antibacterial agents (14). [...] Strains that overproduce the marA or soxS protein (which is a marA homologue) upregulate the AcrAB multidrug efflux pump which pumps out pine oils, organic solvents, triclosan,quaternary ammonium compounds, chloroxanol, and chlorhexidine (4).

We have identified clinical strains of E. coli that are resistant to triclosan because they are also Mar mutants (4). From these and other data, selection for Mar mutants can potentially occur by antibiotics or by antibacterial agents.

Comments

[kalmn.livejournal.com]

your post is interesting to read, but none of the text shows up on my friends page, due to the formatting.

[eub.livejournal.com]

Oops. Guess I have to test frivolous HTML under everybody's friends page style. Frivolous HTML removed, instead. (I hope I got enough of it.)

[beaq.livejournal.com]

I *think* you can defrivolize by enclosing all the frivolity in an empty <div>, or use set_frivolity = false when you're playing in the rafters.

[brokengoose.livejournal.com]

Do you have any idea why shikimic acid is so essential to oseltamivir's production?

In particular, I wonder whether foods that are high in shikimic acid might be useful in flu prevention. (Can't you see the tabloid headlines now?) My instinctive answer is "Yes, but only in quantities so great that they'd have even worse side effects," but that's a wild, uneducated guess.

[eub.livejournal.com]

Do you have any idea why shikimic acid is so essential to oseltamivir's production?

Oseltamivir has stereocenters in three places -- see where the bonds are made of cross-dashes (pointing below the "paper") and of a wedge (pointing above). Making those in the right orientation from scratch is quite hard, but living creatures do it all the time, in quantity, so the usual approach when your target is a structure like this is to work backwards to start from some natural product. Shikimic acid happens to have stereocenters in the same three places on the ring, and has groups on them that a chemist can get a handle on.

In particular, I wonder whether foods that are high in shikimic acid might be useful in flu prevention.

Only by some coincidence, I think. Same central ring as oseltamivir, but they differ in all four functional groups hanging off the ring.

[sheenaqotj.livejournal.com]

I haven't been _personally_ concerned about the avian flu since many viruses don't affect me as badly as other people.

Bacteria, on the other hand, kick my ass. The Z-Pak is the only thing that's brought me back from really bad sicknesses and pneumonia. Completely resistant bacteria... ugh! I don't want to think about the consequences!

[eub.livejournal.com]

Completely resistant bacteria... ugh!

I don't know whether this particular mode of resistance shows up in the real world, or what its effect is. Hm, Google suggests yes, but among lots of others equally or more important. So I'm guessing it's not an emerging problem, but just part of what's already out there -- which is some unfortunate stuff, but not doomsday. As long as people lay off the damn feeding antibiotics to everything, already.

[r-transpose-p.livejournal.com]

I have forwarded your shikimic acid notes to a chemist.

[eub.livejournal.com]

?