Ansamitocin Libraries by Combining Mutasynthesis with Chemical Synthesis; A New Version of Total Synthesis

• Published in: Synlett 2012-06, Vol.23 (10), p.1416-1426
• Main Authors: Taft, Florian, Eichner, Simone, Knobloch, Tobias, Harmrolfs, Kirsten, Hermane, Jekaterina, Kirschning, Andreas
• Format: Article
• Language: English
• Subjects: account; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antineoplastic agents; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Chemistry; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; General aspects; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Medical sciences; Methods. Procedures. Technologies; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties
• ISSN: 0936-5214; 1437-2096
• DOI: 10.1055/s-0031-1290695

Abstract Blocked mutants of Actinosynnema pretiosum , the producer of the highly cytotoxic antitumor agent ansamitocin, serve as powerful tools that allow synthetic chemists to generate natural product libraries. The power of this approach can be dramatically expanded when mutasynthesis is combined with chemical synthesis. This report provides illustrative examples of the application of this strategy to produce libraries based on the ansamycin antibiotics. 1 Introduction 2 Mutasynthesis — A Powerful Strategy for Accessing New Ansamitocin Derivatives 3 Mutasynthesis Combined with Semisynthesis; Further Generalization of a Diversity Concept 4 Mutasynthesis with Advanced Synthetic Intermediates 5 Blocked Mutants as Tools for Biosynthetic Studies of ­Ansamitocins 6 Conclusions