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The German chemist Friedrich Wöhler is generally credited with the first laboratory synthesis of a known organic compound (urea) from inorganic materials. He accomplished this by the simple heating of an inorganic salt, ammonium cyanate (NH4OCN). “I must tell you,” he wrote to his mentor Jöns Jakob Berzelius in 1828, “that I can prepare urea without requiring a kidney of an animal, either man or dog.” While this report may seem relatively minor given the structural simplicity of urea, its impact was revolutionary. For the first time, the preparation and isolation of an organic compound had been achieved in the absence of the elemental “vital force” of living systems previously believed to be required for the construction of all such compounds. This milestone of 19th century organic chemistry was later followed by many others, including Kolbe’s synthesis of acetic acid in 1847 and Fischer’s synthesis of glucose in 1890. With the support of evolving methods for compound separation, purification, and spectroscopic analysis, rapid advances in the sophistication of organic synthesis followed throughout the 20th century, developing in tandem with an ever-deepening understanding of the underlying organic processes associated with living systems. While it is certainly true that syntheses of many structurally complex unnatural compounds of theoretical interest are also among the most remarkable achievements in synthetic strategy, tactical execution, and perseverance, the realm of natural products remains the dominant source for the most challenging and potentially beneficial targets available for such synthetic efforts. Figure 8.1 shows a small selection of some natural (and unnatural) products which have been produced via synthesis over the years, from Wöhler’s time to the present. Note the increasing levels of structural sophistication and stereochemical complexity that have eventually been mastered by practitioners of organic synthesis. In our own time, the traditional boundaries between organic and biological chemistry are disappearing in ways that are likely to transform the design and synthesis of organic molecules, from the construction of synthetic biologicals designed to act as biomarkers, biosensors, or drug delivery agents, to the development of molecular motors, self-replicating macromolecular systems, and even synthetic life forms. |
