The Importance of Chemical Synthesis

An invitation to join a pharmaceutical company, which is not given lightly, represents an opportunity to join a complex, cooperative enterprise. Within it, synthetic and medicinal chemists are not optional but indispensable, and their role has been likened to a mother s The chemist gives birth to the drug [italics added], but the [physician] supports its first steps (attributed to Foumeau by A Maurois). Indeed, the labor of birthing drugs can earn not only a chemist s salary but a clinician s respect. 

Molecular modification, as it is known, represents some of the work that industrial organic chemists do. It attracted the notice of the cardiologist and Professor of Clinical Medicine Michael J. Halberstam. He wrote, New molecules and drugs derived by chemical modification of active drugs have for 200 years been the source of virtually aU important pharmacotherapeutic advances. While most molecular modification does not result in clinically dramatic improvement, Halberstam went on, most clinically significant improvement results from molecular modification [italics added]. 

This work, necessary as it is to drug discovery and development, does not suffice to bring commercial and therapeutic success, as two industry executives note. Bert Spilker, President of Orphan Medical, and Pedro Cun-trecasas, former President of Parke-Davis, note that a single scientist rarely if ever discovers, develops, and launches a new drug. [Nevertheless,] though the breakthroughs come by a series of small steps, the original idea 

Chemical synthesis remains as important to society as it became during World War II, when the modem pharmaceutical industry originated in its efforts to develop penicillins. Ever since, organic chemists literally have made the drugs that relieve our illnesses. Further examples include the antiinflammatory cortisone, developed in the 1940s to treat arthritis, and the protease inhibitors indinavir, ritonavir, and saquyinavir, introduced in 1995 to suppress the human immunodeficiency virus (HfV). 

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The importance of chemical syntheses of a-amino acids on industrial scale is limited by the fact that the standard procedure always yields the racemic mixture (except for the achiral glycine H2N-CH2-COOH and the corresponding amino acid from symmetrical ketones R-CO-R). A subsequent separation of the enantiomers then is a major cost factor. Various methods for the asymmetric synthesis of a-amino acids on laboratory scale have been developed, and among these are asymmetric Strecker syntheses as well. ... 

About 1890, which was prior to the synthesis of alizarin and indigo, the United States enjoyed a position of organizational superiority because they recognized the importance of chemical engineering as an independent discipline. 

Chiral recognition by CyDs is of primary importance for the pharmaceutical industry since the second enantiomer of a drug, usually present as 50% impurity as the result of chemical synthesis, can be harmful. Therefore, an effective preparative separation of enantiomers is one of the important goals of applied CyD research since at present it has not reached the industrial scale. Today the main CyD application in the pharmaceutical industry is their use as drug carriers, since CyD containers in most cases stabilize and solubilize the included drugs (see, how-... 

Aromaticity is one of the most useful concepts in chemistry. We teach it in undergraduate courses, and we need it in our everyday work as chemists. To abandon this concept because it doesn t have a rigorous physical basis would mean that we would lose a very important tool to interpret and predict the properties of molecules on a qualitative basis. A theoretical physicist or chemist might argue that nowadays properties of molecules can be predicted with almost chemical accuracy. So why do we need qualitative concepts like aromaticity Ifs because chemistry is about more than the prediction of numbers. Chemistry is not a science in a strictly reductionist definition. There is a large part of an engineering-type of reasoning involved in chemistry. The analytic part of chemistry may be covered by quantum mechanics, but the constructive part is not accessible to theoretical methods (e.g., try to set up a wavefunction to solve the problem of chemical synthesis). 

Existence/nonexistence of a compound is certainly an important topic of chemistry, but depends on the state-of-the-art of chemical synthesis and survey of natural occurrence. In Chapters 7 and 8 we shall consider other properties of compounds, including less variable properties. We shall try to deduce experimental properties horn the chemical structure and vice versa. For this purpose it is crucial to generate in silica molecular structures with prescribed structural properties in silica, i.e. to generate virtual molecular libraries. The most important tools for this task will be described in Chapter 5. 

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