通常の化学反応は、二種類の基質を結合させて新しい化合物を作るものである。
その一方で、多成分連結反応(Multicomponent Reactions MCRs)とは、3種類以上の成分をひとつのフラスコで反応させて化合物を得る反応形式である。
極少ないステップ、ワンポット反応にて構造多様性・極性官能基に富む鎖状化合物や複素環化合物が得られる。このため、医薬品開発の分野で特に需要のある反応形式とされる。
コンビナトリアル化学、多様性指向型合成、ハイスループットスクリーニングなどの考え方と親和性が高い。
反応の定義上、最終生成物には全ての構成成分(もしくはその一部)が含まれなくてはならない。このため、ルイス酸などの促進剤・触媒、溶媒などは、成分数としてカウントしないのが通例である。
イソニトリル、イミニウム中間体経由の反応は、MCRとなることが多い。
例えばPasserini反応、Ugi反応、Mannich反応、Strecker反応、Hantzchピリジン合成、Biginelli反応などはその典型例である。このような反応においては、脱離物も水だけであることが多く、アトムエコノミーも高くなる傾向がある。
関連文献
<総説>
[1]”Multiple-Component Condensation Strategies for Combinatorial Library Synthesis”
Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123. DOI: 10.1021/ar9502083
[2] “Recent progress in the chemistry of multicomponent reactions”
Ugi, I. Pure. Appl. Chem. 2001, 73, 187. DOI: 10.1351/pac200173010187
[3] “The discovery of new isocyanide-based multi-component reactions”The chemistry of multicomponent reactions (MCRs) and isocyanides belongs to three periods: In the century 18591958, isocyanide chemistry was moderately active and was separate from the classical name reactions of the MCRs. In the next period, isocyanides became well available, and MCRs of isocyanides became the most variable way of forming chemical compounds. The year 1993 began a new era of the formation and investigation of the products and the libraries of the Ugi reaction (U-4CR) and higher MCRs of the isocyanides. This chemistry is primarily accomplished in the industrial search and preparation of new pharmaceutical and plant-protecting products.
Domling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3168.
Domling, A. Curr. Opin. Chem. Biol. 2000, 4, 318. DOI:10.1016/S1367-5931(00)00095-8
[4] “Chemistry and Biology Of Multicomponent Reactions”Multi-component reactions are finding increasing use in the discovery process of new drugs and agrochemicals. Some years ago they were considered as highly exotic types of organic reactions. Recently, many groups have realized that the field of multi-component reactions is full of new opportunities. These comprise fast and efficient production of small-molecular-weight compound libraries, highly atom-economic chemistry, very large chemical libraries, improvements in total synthesis, and applications in bioconjugate chemistry, as well as in related fields (e.g. chemical biology).
Domling, A.; Wang, W.; Wang, K, Chem. Rev. 2012, 112, 3083. DOI: 10.1021/cr100233r
関連書籍
[amazonjs asin=”3527308067″ locale=”JP” title=”Multicomponent Reactions”][amazonjs asin=”B00HD11ZF8″ locale=”JP” title=”Development of New Radical Cascades and Multi-Component Reactions: Application to the Synthesis of Nitrogen-Containing Heterocycles (Springer Theses)”][amazonjs asin=”B00F5TMITW” locale=”JP” title=”MCR 2009: Proceedings of the 4th International Conference on Multi-Component Reactions and Related Chemistry, Ekaterinburg, Russia: 699 (Advances in Experimental Medicine and Biology)”]
関連リンク
- 多成分反応 (PDF; Sigma-Aldrich)
- Multicomponent reaction (organic-chemistry.org)
- Multicomponent Reaction: highlight (organic-chemistry.org)
- Multicomponent Reaction – Wikipedia
