Total synthesis
Total synthesis refers to the laboratory process of constructing complex organic molecules from simpler chemical compounds through a series of chemical reactions. This intricate method allows chemists to create substances that are often found in nature, playing a crucial role in the development of significant medicinal compounds. The practice began in the early nineteenth century, evolving from simple one-step processes to more complex multi-step syntheses by the mid-twentieth century. Notable achievements in total synthesis include the creation of quinine, penicillin, and insulin, which have had a profound impact on healthcare.
Chemists typically start by isolating the target molecule, analyzing its properties, and devising a strategy for synthesis, often working backward to identify the simplest pathway from the desired compound to the starting materials. The efficiency of total synthesis is measured by the number of steps required to produce the final product, with modern advancements often seeking to minimize these steps. This field continues to evolve, contributing to the production of various pharmaceuticals and providing insights into the underlying principles of chemical reactions.
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Total synthesis
Total synthesis is the chemical construction of a complex organic molecule from simpler chemical compounds. The process is performed in a laboratory through a progressive chain of chemical reactions that eventually leads to the intended molecule. The starting compounds used in total synthesis are most often naturally produced substances. Scientists first began to produce, or synthesize, chemical substances in the nineteenth century. It was not until the mid-twentieth century that chemists were able to string together the more complex reactions needed for total synthesis. The process has led to the mass production of many important medicines and drugs, including bacteria-fighting penicillin and the hormone insulin.
Background
Chemical substances, such as the chemical elements or chemical compounds, are found in nature or can be created through the forming or breaking of chemical bonds at the atomic level. These reactions can occur naturally or be produced in a laboratory setting. All chemical elements are made up of atoms, the smallest units of matter. The atoms are themselves made up of three smaller particles called electrons, protons, and neutrons. Electrons are negatively charged particles that orbit a nucleus of protons and neutrons. It is the electrons that are primarily responsible for the formation of chemical bonds.
Electrons circle the atomic nucleus in a series of shells. The outer shell of an atom determines how well it bonds with other elements. Atoms with a full outer electron shell are more stable and generally do not bond well with other atoms. An atom with less than the maximum number of electrons in its outer shell is more likely to bond with a similar atom in an effort to fill out both their outer shells. Some atoms bond more easily than others. Carbon (C) has four out of a maximum eight electrons in its outer shell. As a result, carbon atoms bond well with many other atoms.
A molecule forms when the electrons of two or more atoms join together. Chemical compounds form from the bonding of atoms or molecules of two or more chemical elements. For example, oxygen (O) and hydrogen (H) are both chemical elements. When two hydrogen atoms and one oxygen atom bond together, it forms the chemical compound known as water (H2O). Common table sugar is a compound made up of twelve carbon atoms, twenty-two hydrogen atoms, and eleven oxygen atoms (C12H22O11).
Overview
In the early nineteenth century, scientists began to manipulate the chemical bonds of certain substances to synthesize new substances. These early examples involved simple, one-step processes. In the early twentieth century, researchers attempted more complex syntheses by breaking and reforming a series of chemical bonds to gain a desired result. German chemists Paul Rabe and Karl Kindler are often credited with using total synthesis to create the compound quinine in 1918. Quinine is used as a drug to treat the disease malaria. Rabe and Kindler started with quinotoxine, a substance obtained from the bark of a South American tree. Their process involved three steps.
The basic path toward total synthesis generally involves first isolating a target molecule, determining its chemical characteristics, and developing a strategy to synthesize it. Chemists often work backward, tracing the steps along the path from target molecule to starting point. Because total synthesis involves breaking specific chemical bonds and forming new ones, scientists must often follow a complex sequence to achieve success. Typically, each step involves changing only one of a molecule's several chemical bonds at a time. The goal of successful total synthesis is to accomplish the transformation from starting substance to end result in as few steps as possible.
One of the most influential scientists in the field of total synthesis was Robert Burns Woodward, an organic chemist at Harvard University. In the 1940s, Woodward and colleague William von Eggers Doering were celebrated as being the first to synthesize quinine, although it was later recognized that Rabe and Kindler had accomplished the feat decades earlier. Throughout the 1950s, 1960s, and 1970s, Woodward successfully synthesized a number of chemical substances, including cholesterol, the pesticide ingredient strychnine, and high blood pressure medication reserpine. His work earned him the 1965 Nobel Prize in Chemistry.
In the late 1920s, Scottish scientist Alexander Fleming found that a mold called Penicillium notatum could be used to kill some bacteria that were harmful to humans. From his discovery, Fleming developed the antibiotic penicillin. By the 1940s, penicillin was in high demand as an effective treatment for a variety of bacterial illnesses. Scientists in the United States and the United Kingdom had spent millions of dollars trying to find a way to synthesize the medicine, but they met with little success. In 1957, chemist John C. Sheehan at the Massachusetts Institute of Technology discovered the path to create a type of penicillin known as penicillin V, the drug used to treat strep throat. Sheehan began with a form of basic penicillin and used a five-step synthesis process to achieve his goal.
Many early successes in total synthesis have been improved upon in the modern era, typically by reducing the number of steps needed to produce a result. Total synthesis has been used to develop new forms of quinine and reserpine. It has also been used in producing synthetic versions of the painkiller morphine and the cancer drug Taxol. The procedure is also commonly used to synthesize insulin. Insulin is a hormone usually produced by the body to regulate blood sugar. Too little insulin can result in high levels of sugar in the blood and cause a serious illness known as diabetes. Synthetic insulin was developed in the 1960s and 1970s and was first used by human patients in 1982.
Bibliography
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