Click chemistry

Click chemistry is a concept introduced by K. Barry Sharpless in 2001 and describes chemistry tailored to generate substances quickly and reliably by joining small repeating units together as nature does. In biochemistry, after all, proteins are made from repeating amino acid units and sugars are made from repeating monosaccharide units. The connecting units are based on carbon - hetero atom bonds C-X-O rather than carbon - carbon bonds. In addition, enzymes ensure that chemical processes can overcome large enthalpy hurdles by division into a series of reactions each with a small energy step. Mimicking nature in organic synthesis of new pharmaceuticals is essential given the large number of possible structures.

Related Topics:
K. Barry Sharpless - Biochemistry - Protein - Amino acid - Monosaccharide - Hetero atom - Enthalpy

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In 1996 Guida calculated the size of the pool of drug candidates at 1063, based on the presumption that a candidate consists of less than 30 non-hydrogen atoms, weights less than 500 daltons, is made up of atoms of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, chlorine and bromine, and is stable at room temperature and stable towards oxygen and water. Click chemistry in combination with combinatorial chemistry, high-throughput screening and building chemical libraries speeds up new drug discoveries by making each reaction in a multistep synthesis fast, efficient and predictable.

Related Topics:
Daltons - Room temperature - Combinatorial chemistry - High-throughput screening - Chemical libraries - Multistep synthesis

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A chemical transformation that is part of click chemistry obeys the following criteria:

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• application modular and wide in scope
• obtains high chemical yield
• generates inoffensive byproducts
• is stereospecific
• simple reaction conditions
• has readily available starting materials and reagents
• no solvent involved or a benign solvent (preferably water)
• easy product isolation by crystallisation or distillation but not preparative chromatography
• physiologically stable
• large thermodynamic driving force > 84 kJ/mol for a fast reaction with a single reaction product. A distinct exothermic reaction makes a reactant "spring loaded".
• high atom economy

Chemical reactions that fit the bill are:

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• cycloaddition reactions, particularly the Huisgen 1,3-dipolar cycloaddition as well as Diels-Alder reactions
• nucleophilic substitution especially to small strained rings like epoxy and aziridine compounds
• carbonyl-chemistry-like formation of ureas and amides but not reactions of the aldol type due to low thermodynamic driving force.
• addition reactions to carbon - carbon double bonds like epoxidation and dihydroxylation.

Efficient click chemistry is also exemplified by petrochemicals. In hydrocarbon cracking, small linear alkanes are stripped of hydrogen to form alkenes. Cracking is an endothermic process but the energy expanded is stored in the olefin because olefin reactions, like hydroformylation and Diels-Alder reactions, are very exothermic.

Related Topics:
Petrochemical - Cracking - Endothermic - Hydroformylation - Diels-Alder reaction - Exothermic

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Click chemistry: References ►