title: What can a chemist learn from nature's macrocycles?--a brief, conceptual view.
abstract: Macrocyclic natural products often display remarkable biological activities, and many of these compounds (or their derivatives) are used as drugs. The chemical diversity of these compounds is immense and may provide inspiration for innovative drug design. Therefore, a database of naturally occurring macrocycles was analyzed for ring size, molecular weight distribution, and the frequency of some common substructural motifs. The underlying principles of the chemical diversity are reviewed in terms of biosynthetic origin and nature's strategies for diversity and complexity generation in relation to the structural diversity and similarities found in the macrocycle database. Finally, it is suggested that synthetic chemists should use not only nature's molecules, but also nature's strategies as a source of inspiration. To illustrate this, the biosynthesis of macrocycles by non-ribosomal peptide synthetases and terpene and polyketide cyclases, as well as recent advances of these strategies in an integrated synthesis/biotechnology approach are briefly reviewed.
authors.affiliation: Leibniz-Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany, wessjohann@ipb-halle.de
authors.forename: Ludger A
authors.initials: LA
authors.lastname: Wessjohann
authors.forename: Eelco
authors.initials: E
authors.lastname: Ruijter
authors.forename: Daniel
authors.initials: D
authors.lastname: Garcia-Rivera
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brandt
mesh_terms: D001685:Biological Factors / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D015195:Drug Design; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001685:Biological Factors; D047028:Macrocyclic Compounds