Macrocycles rapidly produced by multiple multicomponent reactions including bifunctional building blocks (MiBs).
Naturally occurring macrocycles often exhibit remarkable biological activities and, therefore, constitute an attractive starting point for diversity-oriented synthesis for lead discovery in drug development. Multicomponent reactions have been used for the introduction of chemical diversity in strategies towards macrocycle libraries, mostly by combinational synthesis of a linear precursor combined with a subsequent macrocyclization reaction. The Ugi reaction in particular may be used for the macrocyclization itself as well, and a library of natural product-like macrocycles can be constructed in a single step from simple precursors. The efficiency and versatility of both strategies is immense and is exemplarily illustrated by the construction of small libraries of cyclopeptide alkaloid derivatives and biaryl ether macrocycles. The syntheses of the latter compound group are examples of multiple multicomponent macrocyclizations including bifunctional building blocks (M3iB3 or MiB), of which the Ugi-MiBs and their variations are discussed in more detail.
Wessjohann
Ludger A
LA
Leibniz-lnstitute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany. wessjohann@ipb-halle.de
Ruijter
Eelco
E
D001685:Biological Factors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002625:Chemistry, Organic / Q000379:methods; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation
D001685:Biological Factors; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents