You're Carding me for Cough Medicine?

Due to a really bad tickling cough, I haven’t been able to sleep in about a week.  When my cough began 2 weeks ago, I started taking generic, run of the mill cough medicine.  Then as the coughing got worse, I switched to a cough medicine with dextromethorphan.  Besides the fact that I had to present multiple forms of ID to the awful cashier at Wal-Mart (apparently there's a “problem wiff meff” in my fair city…vida infra), it did the trick for the day, but really didn’t help at night.

I don’t usually get bad coughs.  The last time I was “blessed” with the plague, the University nurse practicioner wrote me two scripts for azithromycin and cough medicine with codeine (surprisingly I wasn’t asked to take a pregnancy test—usually par for the course at our health center).  Apparently codeine, though a controlled substance, is an excellent cough suppressant (though its true therapeutic value has been called into question; Pulmonary Pharmacology 1996, 9, 293–297).  I remember that codeine cough syrup seemed to help last time, but we’ll see what happens.

The reason why codeine is a controlled substance in the US is because of it is classified as a narcotic and is structurally similar to morphine.  Several webpages I’ve read note that codeine is manufactured by chemoselective methylation of the phenol in morphine (extracted from opium plants).  Codeine is apprently less potent than morphine, however one of the first biotransformations codeine undergoes upon entering the body is (you guessed it) demethylation.  I think Wikipedia claims that ~12% of the codeine ingested into your body is converted to morphine.

All of this relates back to synthetic organic chemistry.  Morphine (a lot like quinine) is a “proof of concept” synthetic target; it's often used to put new synthetic methodologies to the test due to its structural complexity.  

Morphine contains a complicated pentacyclic skeleton with a central quaternary center and thus represents an excellent challenge to synthetic chemists.  Among the best syntheses are Fukuyama’s approach (intramolecular Mannich-type reaction; Org. Lett. 2006, 8, 5311-5314) and Trost’s one of several routes (particularly Pd-catalyzed asymmetric allylation; J. Am. Chem. Soc. 2005, 127, 14785–14803).  I like Fukuyama’s synthesis for two reasons.  First, the molecular complexity dramatically increases over the course of one reaction.  In refluxing, acidic methanol, they were able to form the final two rings in one step.  Second, you cannot go wrong (economically speaking) with refluxing methanol and hydrochloric acid.  They’re cheap reagents and my hat's off to someone who doesn’t go out and buy a specialized chemical (e.g. using DAST instead of TBAF).   

Hope everyone has a great weekend!

P.S. Sorry about the lack of posts this past month.  “The Man” has given me a date I’m trying to stick to, so it translates to extra time in the lab.