Click chemistry

The concept of click chemistry was founded in 2001 by K. Barry Sharpless with Hartmuth Kolb and MG Finn and describes a way to synthesize faster and more targeted target molecules from smaller units, similar to the nature it performs.

Explanation

In biochemistry, proteins from individual amino acids and polysaccharides from individual sugar units, the monosaccharides are formed. The interconnecting units consist usually of carbon - heteroatom bonds. In nature, enzymes overcome the high enthalpy of individual chemical reactions, by carrying them in a series of smaller individual steps of lower enthalpy.

1996 calculated Guida the number of molecules for a potential pharmaceutical application of 1063, based on the assumption that this is less than 30 " non- hydrogen " containing less than 500 daltons weigh only the elements hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, chlorine and bromine are made, and are stable both at room temperature as well as to oxygen and water. Click chemistry can significantly accelerate drug development by pharmaceutical agents, by can be a major problem in the development of a drug, the synthesis of the drug itself, broken down into many smaller problems, in combination with combinatorial chemistry, high throughput screening and the development of chemical libraries.

A chemical transformation must satisfy the following criteria by click chemistry:

  • Modular design and wide applicability
  • High yields
  • Safe and non-interfering by-products
  • Stereospecifically
  • Simple reaction conditions
  • Readily available and inexpensive reagents
  • Solvents that a simple product isolation allow (preferably water)
  • Simple work-up and isolation of the product by crystallization or distillation (not chromatographic method )
  • High thermodynamic driving force ( enthalpy > 84 kJ / mol) in order to ensure a quick reaction to a single reaction product
  • High atom efficiency

Chemical reactions that meet these criteria are:

  • The cycloaddition reactions, especially Cu (I) catalyzed Huisgencycloaddition and the Diels-Alder reaction,
  • Nucleophilic substitutions, especially those of small strained rings such as epoxides or aziridines
  • Carbonylähnliche formation of ureas and amides, due to the low enthalpy of formation but not aldol
  • Addition reactions to carbon-carbon double bonds, such as epoxidation.

Swell

  • Hartmuth Kolb, MG Finn, K. Barry Sharpless: Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew. Chem 2001, vol 113, p 2056; doi: 10.1002/1521-3757 ( 20,010,601 ) 113:11 < 2056 :: AID- ANGE2056 > 3.0.CO; 2 -W.
  • Hartmuth Kolb, MG Finn, K. Barry Sharpless: Click Chemistry: Diverse Chemical Function from a Few Good Reactions, Angew. Chem Int. Ed. 2001, vol 40, p 2004; doi: 10.1002/1521-3773 (20010601) 40:11 < 2004 :: AID- ANIE2004 > 3.0.CO; 2-5.
  • W. C. Guida et al. Med Res Rev. p 3 1996.
  • Chemical Reaction
Atom economy 1,3-Dipolar cycloaddition Diels–Alder reaction Digital Object Identifier Integrated Authority File
193988
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