1. Option D: Medicines and Drugs Unit D.3.3: Structural Comparisons of Analgesics Chemistry SL Dixon Adair

2. Introduction to Opiates “The most important naturally occuring strong analgesics are morphine and codeine found in the opium poppy. “Morphine, codeine and semi-synthetic opiates…, such as heroin, all possess the same basic structure.” Source: Textbook

3. Structural Diagrams “In codeine one of the hydroxyl groups has been substituted for an ether group…” (Textbook) The opiates shown here are naturally occuring.

4. Codeine “Codeine (INN) or methylmorphine is an opiate used for its analgesic, antitussive and antidiarrheal properties. It is by far the most widely used opiate in the world…It is one of the most effective orally- administered opioid analgesics and has a wide safety margin. It [has] from 8 to 12 percent of the strength of morphine in most people…” (Edinformatics) “Codeine is an alkaloid found in opium poppy, a plant in the papaveraceae family that has been cultivated and utilized throughout human history. Codeine can also be acquired in saps from other poppies such as Papaver bracteatum, in concentrations ranging from 0.3 to 3.0 percent.alkaloidopium poppypapaveraceaePapaver bracteatumpercent While codeine can be extracted from opium, most codeine is synthesized from morphine through the process of O-methylation. [SEE PREVIOUS SLIDE] It was first isolated in 1832 in France by Jean-Pierre Robiquet.” (Wiki)morphinemethylationFranceJean-Pierre Robiquet

5. Morphine “Morphine (INN) (pronounced / ˈ m ɔ rfi ː n/) (MS Contin, MSIR, Avinza, Kadian, Oramorph, Roxanol) is an extremely potent opiate analgesic psychoactive drug, is the principal active ingredient in Papaver somniferum (opium poppy, or simply opium)…”INN/ ˈ m ɔ rfi ː n/ potentopiateanalgesicpsychoactive drugactive ingredientPapaver somniferumopium poppy opium “In clinical medicine, morphine is regarded as the gold standard, or benchmark, of analgesics used to relieve severe or agonizing pain and suffering.”painsuffering “Morphine acts directly on the central nervous system (CNS) to relieve pain. Morphine has a high potential for addiction; tolerance and both physical and psychological dependence develop rapidly.”central nervous systempainaddiction tolerancephysical psychologicaldependence Source for above: Wikipedia

6. Heroin: Introduction “Diamorphine (heroin) is more powerful and addictive than morphine.” (Textbook) Heroin is a semi-synthetic opiate. Definition of Semi-Synthetic: “Semisynthesis" or partial chemical synthesis is a type of chemical synthesis that uses compounds isolated from natural sources (e.g. plant material or bacterial or cell cultures) as starting materials. These natural biomolecules are usually large and complex molecules.” (Wikipedia)chemical synthesisnatural sources plantbacterial cell cultures biomoleculesmolecules Two ester groups, hence the name “Diamorphine” (more properly known as diacetylmorphine) (commonly known as heroin)

7. Heroin: The Name “Heroin, or diacetylmorphine (INN), also known as diamorphine (BAN), is a semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy. It is the 3,6-diacetyl ester of morphine (di (two)-acetyl-morphine).” (Wiki)INNBANsemi-synthetic opioid drugmorphineopium poppydiacetylesterdiacetylmorphine Diacetyl means two acetyl groups, but what is an “acetyl” group or an acetate? “An acetate (IUPAC name: ethanoate) is either a salt or an ester of acetic acid.” (Wiki)IUPACsaltesteracetic acid Acetic Acid (or ethanoic acid) is seen in the diagram to the right. Ethanoic anhydride is simply “dehydrated” 2 CH3COOH which turns into ethanoic anhydride, after losing its OH. Q: Why is this important? A: The diacetyl part of heroin is what distinguishes it from its original source: morphine.

8. Heroin: How it’s Made “…heroin is the diester [i.e. two esters] formed from the condensation of morphine with ethanoic anhydride.” The process described above is done by reflux. Reflux is a technique involving the condensation of vapors and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations. condensation distillations Diesterification with ethanoic anhydride, above + 2 Ethanoic Acid

9. Ethical Issues As we can see, codeine, morphine, and heroin all possess the same basic structure, yet their “slight” chemical differences make them have very different effects on humans. Where do we draw the line between what derivatives of morphine can/should be used? Is there such thing as an analgesic which is TOO strong, such as heroin?

10. Additional Information Poppy seed is an oilseed obtained from the opium poppy (Papaver somniferum). The tiny kidney-shaped seeds have been harvested from dried seed pods by various civilizations for thousands of years. The seeds are used, whole or ground, as an ingredient in many foods, and they are pressed to yield poppyseed oil. (Wiki)oilseedopium poppykidneypoppyseed oil To some extent harvesting for poppy seeds is in conflict with harvesting for opium. Poppy seeds of superior quality are harvested when they are ripe, after the seed pod has dried. Traditionally, opium is harvested while the seed pods are green and their latex is abundant, but the seeds have just begun to grow. (Wiki)

11. Thank You