Chemistry Is Everywhere: Actual Yields in Drug Synthesis and Purification

Many drugs are the product of several steps of chemical synthesis. Each step typically occurs with less than 100% yield, so the overall percent yield might be very small. The general rule is that the overall percent yield is the product of the percent yields of the individual synthesis steps. For a drug synthesis that has many steps, the overall percent yield can be very tiny, which is one factor in the huge cost of some drugs. For example, if a 10-step synthesis has a percent yield of 90% for each step, the overall yield for the entire synthesis is only 35%. Many scientists work every day trying to improve percent yields of the steps in the synthesis to decrease costs, improve profits, and minimize waste.

Even purifications of complex molecules into drug-quality purity are subject to percent yields. Consider the purification of impure albuterol. Albuterol (C₁₃H₂₁NO₂; accompanying figure) is an inhaled drug used to treat asthma, bronchitis, and other obstructive pulmonary diseases. It is synthesized from norepinephrine, a naturally occurring hormone and neurotransmitter. Its initial synthesis makes very impure albuterol that is purified in five chemical steps. The details of the steps do not concern us; only the percent yields do:

That is, only about one-fourteenth of the original material was turned into the purified drug. This gives you one reason why some drugs are so expensive; a lot of material is lost in making a high-purity pharmaceutical.