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Molecular Diversity

, Volume 9, Issue 1–3, pp 159–169 | Cite as

Macrocycles rapidly produced by multiple multicomponent reactions including bifunctional building blocks (MiBs)

  • Ludger A. WessjohannEmail author
  • Eelco Ruijter
Perspective

Abstract

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.

Keywords

diversity-oriented synthesis macrocycles multicomponent reactions natural products Ugi-reaction 

Abbreviations

DOS

diversity-oriented synthesis

MCR

multicomponent reaction

MiB

(= M3iB3 = MMMiBBB) multiple multicomponent macrocyclization/macrocycle including bifunctional building blocks

MUMBI

multiple Ugi macrocyclization using bifunctional isonitriles

RCM

ring-closing metathesis

U4CR

Ugi four-component reaction

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Bioorganic Chemistry, Weinberg 3Leibniz-Institute of Plant BiochemistryD-06120 Halle, (Saale)Germany

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