Click Chemistry: Diverse Chemical Function from a Few Good R
发布日期：2022-10-07 20:54 浏览次数：
Click Chemistry: Diverse Chemical Function from a Few Good Reactions
First published: 28 May 2001
Abstract
Just a handful of good reactions are needed to assemble vast numbers of highly diverse organic molecules. (The graphic shows a simple example.) Yet, this easily accessible structural universe has not been mined by the medicinal chemistry community for its nuggets of desirable function. The requirements for the best reactions that can be employed, examples of such processes, and the philosophy that underlies their use are discussed in this review.
Abstract
Examination of nature's favorite molecules reveals a striking preference for making carbon–heteroatom bonds over carbon–carbon bonds—surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon–heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C−C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C−X−C), an approach we call “click chemistry”. Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect “spring-loaded” reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.
