Abstract

Prostaglandins are a family of naturally occurring substances found in animals and humans. They are produced from 20 carbon fatty acids in vivo and play important and diverse roles in both health and disease. Unlike circulating hormones, prostaglandins are synthesized and released by most tissues, act near their site of synthesis, and then are rapidly inactivated by metabolic enzymes. They are among the most potent substances known and exert regulatory influences on virtually all tissues and organs.

Because of their diverse biological effects and their potential as therapeutic agents, prostaglandins underwent intense scrutiny following their structural elucidation and availability in the early 1960s. Both academic and industrial laboratories studied their biosynthesis, metabolism, physiological and pharmacological effects, and their chemical and physical properties. The total synthesis of prostaglandins presented formidable challenges. Because of their structural and stereochemical complexity and chemical instability, they provided a strong impetus to the development of new synthetic methodologies. The prostaglandins and many analogues are available by total synthesis and some have reached the marketplace as therapeutic agents. Examples are prostaglandin E₁ (PGE₁), used in cardiovascular and reproductive indications; analogues of prostaglandin F₂ , used in estrus synchronization in farm animals; misoprostol, an analogue of PGE₁, used in the treatment of ulcers; prostacyclin and some of its analogues, used for cardiovascular diseases; and latanoprost, used in the treatment of glaucoma.