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

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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.

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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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Authors and Affiliations

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

    Ludger A. Wessjohann & Eelco Ruijter

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  1. Ludger A. Wessjohann
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  2. Eelco Ruijter
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Correspondence to Ludger A. Wessjohann.

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Wessjohann, L.A., Ruijter, E. Macrocycles rapidly produced by multiple multicomponent reactions including bifunctional building blocks (MiBs). Mol Divers 9, 159–169 (2005). https://doi.org/10.1007/s11030-005-1313-y

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  • DOI: https://doi.org/10.1007/s11030-005-1313-y

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