Lidocaine

CHEMISTRY 338 THE SYNTHESIS OF LIDOCAINE Lidocaine (1) is the common name of an important member of a category of drugs widely used as local anesthetics. Trade names for this substance include Xylocaine, Isocaine, and Anestacon, and its systematic chemical name is 2-(diethylamino)-N-(2’,6’dimethylphenyl)acetamide. Two other members of this same family are procaine (2), known more commonly by the trade name Novocaine, and Isocaine (3). Isocaine, in addition to having applications as a topical anesthetic, is commonly found in “sunscreens” that are applied to the skin to prevent sunburn because it absorbs the ultraviolet rays that are responsible for the burning of skin. Similarly, 1 and 2 are used in ways other than for anesthesia. Both are effective in the treatment of arrhythmia, a condition involving erratic beating of the heart, although 2 must be converted to the amide 4 in order to maximize its effectiveness in this application; this simple chemical transformation increases the drug’s half-life under biological conditions and suppresses the rate at which it enters the central nervous system, an undesired property. Interestingly, the antiarrhythmic properties of these compounds were discovered accidentally by cardiologists during the course of surgical procedures for which their anesthetic applications were needed.

CH3 H N O CH3 O N CH3 CH3 H2N O N CH3 CH3

Lidocaine (1)

Procaine (2)

O O H2N

Isocaine (3)

CH3 N CH3 HN H3C O

O O N

CH3 CH3

4

It should not be too surprising to learn that many biologically active compounds that are available today as a result of the synthetic skills of chemists have molecular features that mimic those found in natural products. Compounds 1-4 can be considered to be structural mimics of cocaine 5, a heterocyclic natural product found in the coca plant that is native to South America. Unfortunately, cocaine has addictive as well as anesthetic properties, so one of the more compelling reasons to develop...