That’s right. I said it. SHIT. It’s what we all do and, for some of us, it’s the best part of our day. Nothing quite like relaxing on the porcelain throne, flipping through the latest SciAm (or CEN) and droppin’ some ripe deuces. My own personal theory on why pooping is so fun is because of all the various organs the turd caresses on its way out. But that’s waaaaay off point. This post is about a drug that makes you shit. BAD. Like horribly bad. Like Ratemypoo.com bad. That drug’s name is Alli and, if there’s any truth in advertising, you’d rather bunker with the enemy.

Orlistat is an interesting drug and here in the good old YOU ESS OF EH, we can get it over the counter. Alli does what it says it does: it helps people loose weight. It does it without all the hyper jittery super tense bullshit you get from taking most apatite suppressants because it doesn’t work on the CNS. Indeed, it’s never even taken up by the body.

To understand how Orlistat works, we must first understand how fatness happens, biochemically at least. You see, when you cook fatty foods you do various chemical reactions that make food tastier (including hydrolysis of the fat) but nevertheless, a substantial amount remains as unmolested triglyceride. The intestines poorly (or don’t) absorb triglycerides and they must be broken into their constituent fatty acids via triglyiceride lipases. From there, the miracle of fatness occurs where the fatty acids are shunted around the body until they finally find their way into a hilarious and gross picture of you sitting at your computer:
fatamericans.png

The bacteria, Streptomyces toxytricini, which secretes the compound lipstatin was discovered one day and the structure of the little guy was elucidated. Lipstatin actually irreversibly bound to lipases and prevented them from breaking down triglycerides. The intestines weren’t able to break them down and the triglycerides would pass through the bowl into the poor victim’s underwear as a gross orange oil:
ohnoespoop.png

Lipstatin turns out to be too unstable and/or expensive to make and the hydrogenated product is the commercially marketed one. Thus, the synthesis and structure of Orlistat is straight forward:
synthesisoforlistat.png

From an article by Fernand Schneider (DOI: 10.1002/hlca.19870700124):

The synthesis of (Orlistat) starts from the known keto ester which, on condensation with dodecanal, gave (the next) compound. Protection of the alcohol function as its tetrahydropyranyl ether and reduction of the keto group gave (a) hydroxy ester. Saponification and ring closure of the resulting β-hydroxy acid with benzenesulfonyl chloride in pyridine yielded β-lactones. After deprotection of the OH group, the resulting mixture of racemic hydroxy-β-lactones was separated by chromatography into racemic cis-β-lactones which were discarded and into racemic trans-β-lactones. Esterification with (S)-N-formylleucine using Mitsunobu’s conditions (inversion of configuration of alcohol) yielded two diastereoisomeric esters.) One of the four diastereoisomers, was identical with tetrahydrolipstatin (hydrogenated lipstatin – aka Orlistat) obtained from natural sources.

The efficacy of the drug appears sound, but it is opposed (as all OTC drugs are) by some faction of people who have nothing better to do then bitch about a drug that, at its worst, makes you shit yourself. Aspirin still makes children retarded, btw. Just thought I’d toss that out there. Does it make you poop yourself? Yes. Yes, it does. And guess what you’re pooping – fat. It’s just like shitting Crisco or butter. Imagine, right now, trying to wipe a schmear of butter off your butthole. Sounds like a challenge doesn’t it? It quickly spreads to the cheeks if it wasn’t broadcast there by an ill timed fart. That’s a rather unfortunate side effect. But so is death, which happens to be an apparent side effect of being fat… or living, for that matter.