Click chemistry
The concept of click chemistry was founded in 2001 by K. Barry Sharpless with Hartmuth C. Kolb and MG Finn and describes a way of synthesizing target molecules from smaller units faster and more precisely, similar to the way nature does it.
Explanation
In biochemistry , proteins are formed from individual amino acids and polysaccharides from individual sugar units, the monosaccharides . The connecting units usually consist of carbon- heteroatom bonds . In nature, enzymes overcome the high enthalpy of individual chemical reactions by performing them in a series of smaller individual steps with a lower enthalpy.
In 1996, Guida calculated the number of molecules for a possible pharmaceutical application to be 10 63 , based on the assumption that these contain fewer than 30 "non-hydrogen atoms", weigh less than 500 Daltons , and consist only of the elements hydrogen , carbon , nitrogen and oxygen , Phosphorus , sulfur , chlorine and bromine , and are stable at room temperature as well as to oxygen and water. Click chemistry, combined with combinatorial chemistry , high-throughput screening, and building chemical libraries, can significantly accelerate pharmaceutical research for active pharmaceutical ingredients by breaking down a major problem in drug development, the synthesis of the active ingredient itself, into many smaller problems.
According to the click chemistry, a chemical transformation must meet the following criteria:
- modular and wide range of applications
- high yields
- harmless and non-disturbing by-products
- stereospecific
- simple reaction conditions
- readily available and inexpensive reagents
- Solvents that allow easy product isolation (preferably water)
- simple processing and isolation of the product by means of crystallization or distillation (non-chromatographic processes)
- high thermodynamic driving force ( enthalpy of formation > 84 kJ / mol ) to guarantee a quick reaction to a single reaction product
- high atomic efficiency
Chemical reactions that meet these criteria are:
- The cycloaddition reactions , especially the Cu (I) catalyzed Huisgency cloaddition and the Diels-Alder reaction
- Nucleophilic substitutions , especially those on small strained rings such as epoxides or aziridines
- Carbonyl-like formation of carbamides and amides, but not aldol reactions due to the low enthalpy of formation
- Addition reactions at carbon-carbon double bonds, such as the epoxidation reactions .
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- Hartmuth C. Kolb, MG Finn, K. Barry Sharpless : Click chemistry: diverse chemical functionality with a handful of good reactions. In: Angew. Chem. 2001, vol. 113, p. 2056; doi : 10.1002 / 1521-3757 (20010601) 113: 11 <2056 :: AID-ANGE2056> 3.0.CO; 2-W .
- Hartmuth C. Kolb, MG Finn, K. Barry Sharpless: Click Chemistry: Diverse Chemical Function from a Few Good Reactions. In: Angew. Chem. Int. Ed. 2001, volume 40, p. 2004; doi : 10.1002 / 1521-3773 (20010601) 40:11 <2004 :: AID-ANIE2004> 3.0.CO; 2-5 .