Looking for Absinthe? Better off Drinking Diazinon for the same Effect
(Please don’t take my title literally)
It’s that time of year again: you don’t have a life for the next 4 weeks because you’re teaching roughly 40 h/week while trying to juggle research and getting a paper out the door (in this case, before the Boston ACS meeting). Tensions are running a bit high, and, as a result, I’ve discovered refuge in going out for dinner/drinks with Kerri. So, after experiencing a week of our respective families in direct contact while staring at the incoming task of a month of nonstop teaching, we headed out to the bar with a couple of friend for a few.
The New Orleans-style décor and a few rounds of drinks certainly helped, but the conversation seamlessly evolved from the Air Force and weddings to Bourbon St. and absinthe. Often described as an “awful” but drinkable liquor, there’s lots of mystery encompassing this iconic drink. A simple search on ebay will return results for posters with green demons, sugar spoons and herb kits. There are numerous websites that’ll instruct you on preparing absinthe (beware, it usually takes anywhere from 2 to 4 weeks). If you dig a bit deeper, you’ll probably find a Czech or German distributer that can get you a bottle (should it survive the voyage through US Customs).
The US government has effectively banned absinthe for some time though (1) prohibiting the use of the purportedly “psychoactive” ingredient thujone for consumption purposes (FDA Regulations, Title 21, Chapter 1, Part 172.510) and (2) requiring that all forms of liquor distillation be licensed through the Bureau of Alcohol Tobacco and Firearms (27 Code of Federal Regulations, Part 19). Fortunately, modern versions of the historically controversial liquor are plentiful courtesy of the internet (some that do not include the use of thujone or distillation). Apart from the boring legal ramifications, absinthe, and more importantly, thujone, is coupled with some interesting chemistry, biologically and synthetically speaking.
Thujone is found in many common herbs, in particular wormwoods (of the genus Artemisia) among junipers, mugwort and cedar leaf oil. Misra and Singh reported high concentrations of a-thujone (traditionally found in absinthe at a 5 ppm concentration) in the steam distillation extracts of Artemisia vulgaris, which is native to mountainous regions of India (J. Nat. Prod. 1986, 49, 941). While thujone carries the stigma of being “psychoactive,” (van Goth purportedly severed his ear whilst “inspired” by absinthe) researchers recently demonstrated that both thujone isomers are actually convulsants. Casida and co-workers reported that a-thujone blocks g-aminobutyric acid (GABA) gated chloride channels during metabolism via noncompetitive inhibition (J. Agric. Food Chem. 2001, 49, 1915-1921), which (from what I gather) is a bad thing. Interestingly, though, thujone (and its corresponding analogs) might play a role in the development of a newer, naturally occurring insecticide. It’s been known that GABA receptors are responsible for binding insecticides (in fruitflies) and point mutation of said receptors lead to insecticide resistance (Nature 1993, 363, 449-451).
Both thujone isomers were recently determined to be radical clocks (J. Org. Chem. 2004, 69, 5684-5689) whereby ring-opening of the cyclopropyl moiety indicates a radical pathway. Conversely, rearrangement of thujone to form the phenol carvacrol indicates a cationic path (BTW, phenols stain well on TLC plates with a 1% solution of FeCl3 in MeOH). In 1971, W. S. Bowers noted the insecticidal properties of thujone, which no doubt gave rise to the preparation of a number of derivatives that are currently being studied by entomologists and chemists alike. No doubt, both thujone isomers are also used as starting materials for natural product synthesis (Helv. Chim. Acta 1989, 72, 205-212), as thujone is a magnificent synthon for cyclopropyl moieties (clearly from a medicinal chemistry standpoint).
Thujone is a controversial, yet very interesting molecule. When I was recently asked to make some absinthe for experimental reasons, I promptly noted that the psychoactive effects of thujone are grossly exaggerated; you’ll clearly feel the effect of the alcohol before anything else hits you. Nevertheless, it’s an interesting tonic that’s coupled with interesting chemistry.
As for me and my time issue? I’m procrastinating from setting up 3 parallel reactions that may, for all intents and purposes, prove my boss is right and I’m wrong. Enough wasting time. Any suggestions for future posts?
