The future of organic chemistry

Not all organic chemists can be involved in such exciting projects as the launching of a lifesaving antiviral drug. Some most certainly have to be: resistant bacteria are fast catching up with our current range of antibiotics, and it is teams of organic chemists, in conjunction with biologists, who will be able to erect the next line of defence against these infections. But the chemistry used in such frontline projects is often the product of work by chemists in other institutions who had no idea that it would eventually be used to make a vital drug. Take the millions of lives saved by the synthesis of indinavir, for example. This drug would not have been possible had not the Sharpless and Jacobsen asymmetric epoxidations, the cata lytic asymmetric reduction, and the stereoselective enolate alkylation, along with many of the methods tried but not used in the final synthesis, been invented and developed by organic chemists in academic and industrial research laboratories. Some of the more famous names involved, like Sharpless, Jacobsen, and Noyori, invented new methods, while others modifi ed and optimized those methods, and still others applied the methods to new types of molecules. Yet all built on the work of other chemists. We can delve deeper into one of the steps in the indinavir synthesis. In 1980 Giovanni Casiraghi, a rather less famous chemist from the University of Parma, published a paper in the Journal of the Chemical Society about selective reactions between phenols and formaldehyde. He and his colleagues made the modest discovery that controlled reactions to give salicylaldehydes could be achieved in toluene with SnCl4 as catalyst. The reaction is regioselective for the ortho isomer and the paper described the rather precise conditions needed to get a good yield.

The reaction was also successful for substituted salicylaldehydes. When Jacobsen came to develop his asymmetric epoxidation, he choses lens as his catalysts, partly because they could be made so easily from salicylaldehydes. Jacobsen epoxidation turned out to be the best large-scale method for preparing the cis aminoindanol for the synthesis of indinavir. This process is very much the cornerstone of the whole synthesis. It cannot have entered Casiraghi’s wildest dreams that his work might some day be useful in a matter of life and death. Neither did his four co-workers nor Jacobsen’s more numerous co-workers see clearly the future applications of their work. By its very nature it is impossible to predict the outcome or the applications of research. But one thing is certain: good research and exciting discoveries come from a thorough understanding of the funda mentals of organic chemistry. When Jacobsen’s epoxidation was fully described in 1998–99, the Casiraghi method was abandoned in favour of an even older method discovered in the 1930s by Duff. The remarkable Duff reaction uses hexamethylenetetramine, the oligomer of formaldehyde and ammonia, to provide the extra carbon atom. The now otherwise unknown Duff worked at Birmingham Technical College. Later in 1972, a William E. Smith, working in the GEC chemical laboratories at Schenectady, New York, found how to make the Duff reaction more general and better yield ing by using CF3CO2H as catalyst. Even so, this method gives a lower yield than the Casiraghi method but it uses less toxic reagents (in particularly it avoids stoichiometric tin) and is more suitable for large-scale work. When Duff was inventing his reaction or Smith was modifying the conditions, asymmetric synthesis was not even a gleam in anyone’s eyes. It is impossible even for the inventor to predict whether a discovery is important or not. Where is organic chemistry going next? As we write this chapter, advances are being made in reactions which would have seemed outlandish even just ten years ago. Work published in the years since 2005 has shown, for example, that many reactions of cations can be made to form single enantiomers of products even if they take place just in the vicinity of a chiral anion. Reactions such as the one below, from 2008, promise to revolutionize, yet again, some of the ways in which chemists make chiral compounds.

Finding drugs is a diffi cult job, and the number of new drugs launched each year is dropping as it becomes harder and more expensive to advance beyond existing treatments and as demands for more stringent safety rightly increase. But new drugs are made because...they can be made! What about all those classes of molecules which have never been made, simply because they have never been needed? Among them may well be molecules that will have all the specifi c attributes we want a potential drug to exhibit. Techniques known as diversity ori entated synthesis are now addressing this idea—how to make and study great families of fund amentally different but potentially revolutionary molecules simply and efficiently. It’s too early to tell, but the hope is that these techniques will provide breakthroughs in the fight against disease by finding completely new ways to attack their causes. Nature is a superb synthetic chemist, and organic chemists have spent the last century exploring efficient ways of building molecular structures more efficiently than nature. Nature builds molecules a certain way because there is no alternative—molecules can be biosynthe sized only if the enzymes to make them exist; enzymes are only made from the same 20 amino acids; amino acids are built into proteins by the same ribosome. The ribosome is the most complex and beautiful molecular structure in the known universe, but it can make only proteins. Chemists, with the periodic table, a supply of raw materials, a laboratory, and their ingenuity can make anything. Sometimes chemists use Nature’s enzymes to do a job, or even force them to evolve to do a job better. By cloning useful enzymes in bacteria and forcing them to mutate, high-speed evolution can be induced, and enzymes can be created which do a job better, faster, or at a different temperature from their original ‘wild type’ ancestors. More often chemists use reactions nature can never use—Rh, Ru, Pd, or phosphine ligands for that matter have never been exploited by any known biological process. What molecules chemists will make next, and how they make them, may determine the well-being of huge numbers of people in the future, but we may well not know it until then.

That future is yours as you continue your studies in organic chemistry beyond the scope of this book, and if you do you will want to read about modern work in more specialized areas. Your university library should have a selection of books on related topics we have only touched on, such as orbitals and chemical reactions, NMR spectroscopy, molecular modelling physical organic chemistry, photochemistry, enzyme mechanisms, biosynthesis, organometallic chemistry, asymmetric synthesis, supramolecular chemistry, and polymer and materials chemistry. This book will equip you with enough fundamental organic chemistry to explore these topics with understanding and enjoyment, and, perhaps, to discover what you want to do for the rest of your life. All of the chemists mentioned in this chapter and throughout the book began their careers as students of chemistry at universities somewhere in the world. You have the good fortune to study chemistry at a time when more is understood about the subject than ever before, when information is easier to retrieve than ever before, and when organic chemistry is more interrelated with other disciplines than ever before.

اخر الاخبار

اخبار العتبة العباسية المقدسة

المجمع العلمي: نحو 300 ألف مستفيد من مشروع القراءة الصحيحة في كربلاء وباقي المحافظات

صحفيون: استحداث المركز الإعلامي لزيارة الأربعين أسهم في تسهيل عمل الإعلاميين وتوفير بيئة مهنية لإنجاز مهماتهم

موكب عميد بني هاشم (عليه السلام) يقدم 4500 وجبة طعام يوميًّا لزائري الأربعين

بمشاركة زائري الأربعين.. إقامة صلاة الجماعة عند مرقد أبي الفضل العباس (عليه السلام)

المزيد

الآخبار الصحية

حجم جزء محدد من الجسم يعكس الصحة العامة ومخاطر الأمراض

تفشي عدوى بكتيرية بفرنسا يحتمل ارتباطها بنوع من الجبن الطري

دراسة حديثة تكشف ما تفعله الشاشات بـ"قلوب الأطفال" !

متلازمة المبنى المريض.. هكذا يتحول تكييف الهواء إلى خطر صحي ؟؟

المزيد

الآخبار التكنلوجية

كيف تتعامل مع حرارة الطقس أثناء القيادة؟

لماذا يجب عليك إيقاف تكييف السيارة قبل إطفاء المحرك؟

دراسة تكشف سببا محتملا وراء زيادة خطر إصابة الأطفال بالتوحد

تشيلي.. العثور على متحجرة حيوان ثديي صغير من زمن الديناصورات

المزيد

مواضيع ذات صلة

The synthesis of oseltamivir

The synthesis of indinavir

Chemistry vs viruses

Terpenes are volatile constituents of plants

Aromatic polyketides

Fatty acids and other polyketides are made from acetyl CoA

Benzyl isoquinoline alkaloids are made from tyrosine

Pyrrolidine alkaloids are made from the amino acid ornithine

Alkaloids are made by amino acid metabolism

The shikimic acid pathway

Phosphoenolpyruvate

Nature’s enolate equivalents: lysine enamines and coenzyme A