Glaser's "Chemistry is in the News"
To Accompany Wade Organic Chemistry 4/e.
Chapter 21. Carboxylic Acid Derivatives

Editorial Comments

Heroin Acetylsalicyclic acid How aspirin works

For aches, pains, and bad coughs, one of the most prescribed and most recommended drugs by doctors is aspirin. However, a hundred years ago, for the same symptoms, heroin could have been prescribed. Heroin and aspirin are both analgesics, and they relieve pain without causing loss of consciousness. Heroin is acetylated morphine and is a member of a class of drugs known as alkaloids. It affects the brain's pleasure system and interferes with the brain's ability to perceive pain. It depresses the activity of the nervous system, including such reflexes as coughing, breathing, and heart rate. It also causes widening of the blood vessels, giving the feeling of warmth and reduces bowel activity. Even with doses sufficiently high enough to produce euphoria, there is little change in coordination, sensation, or intellect. Sedation takes place when taking higher doses, and an overdose results in unconsciousness, coma, and death resulting from respiratory failure. Heroin is highly addictive, and users can develop physical dependence and tolerance to it. Once this happens, positive pleasure is replaced by the necessity of the drug to maintain "normality". Aspirin, a miracle drug of the 20th century, has changed the lives of millions and has made Bayer an industrial giant. It is a painkiller with minor side effects and has remained unique for decades. The aspirin molecule has an acetyl group linked to a salicyclic acid and is derived from white willow bark. Aspirin begins its work when injuries to human tissues release prostaglandins, hormone-like molecules which cause fever and inflammation. The enzyme responsible for production of prostaglandins is PGHS (prostaglandin H2 synthase), containing two protein subunits, each with a long interior channel. Molecules of arachidonic acid, an essential fatty acid, undergoes a chemical transformation in the enzyme's core. There, it converts to molecules of prostaglandin H2. The aspirin molecule prevents this change with its acetyl group, which binds to a site inside the channel, thus blocking the path of the arachidonic acid. Unfortunately, aspirin shuts down all forms of the PGHS enzyme, including the form that protects the stomach lining. Drug companies are currently developing a new class of painkillers that target only the form of PGHS that causes inflammation. New uses of aspirin are discovered all the time. While we can take aspirin for safely, we should keep in mind that, like in the case of heroin, science is notorious for modifying facts. It is possible that the medications we take today might reveal harmful effects in the years to come.

Questions

Question 1: Aspirin is considered to be one of the world's most successful legal drugs. Explain how aspirin relieves pain using the diagram in the editorial comments.

Answer: Chemicals responsible for the process leading to pain in our body are called prostaglandins, and aspirin inhibits production of these chemicals.

Question 2: Draw three resonance structures of aspirin. Which one is the major structure?

Answer:

Major structure

Question 3: The process of making aspirin is important in the pharmaceutical industry. Give one of the ways to synthesize this important drug.

Answer:


An alternative process would be to start with 1-methyl-phenol and oxidize it with KMnO4 to make salicyclic acid (1-hydroxybenzoic acid). Then acylate it with CH3COCl. This will give you acetylsalicylic acid, aka aspirin. Another route to salicyclic acid is by way of 1-diazo-phenol. Add HCN to get 1-cyano-phenol, then hydrolysis with an acid or base catalyst at 200 degrees Celsius.

Question 4: Alkaloids, like morphine and heroin, are important biological compounds. What important functional group do they possess? What do the alkaloids do for organisms that contain them?

Answer: Alkaloids contain amines, which aid bioregulation, neurotransmission, and defense against predators. Because they are involved in a large amount of biological activities, many amines are used in drugs.

Question 5: A hundred years ago, heroin was considered safe and non-addictive substitute for morphine. Today heroin is considered a highly dangerous drug and is also addictive. Even with today's so-called advanced technology, is it still feasible to assume that pharmaceutical companies' research is thorough enough?