Synlett 2012; 23(10): 1416-1426
DOI: 10.1055/s-0031-1290695
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© Georg Thieme Verlag Stuttgart · New York

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

Florian Taft
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011   eMail: andreas.kirschning@oci.uni-hannover.de
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Simone Eichner
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011   eMail: andreas.kirschning@oci.uni-hannover.de
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Tobias Knobloch
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011   eMail: andreas.kirschning@oci.uni-hannover.de
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Kirsten Harmrolfs
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011   eMail: andreas.kirschning@oci.uni-hannover.de
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Jekaterina Hermane
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011   eMail: andreas.kirschning@oci.uni-hannover.de
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Andreas Kirschning*
Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1b, 30167 Hannover, Germany, Fax: +49 (511)762 3011   eMail: andreas.kirschning@oci.uni-hannover.de
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Publikationsverlauf

Received: 03. Dezember 2011

Accepted after revision: 24. Januar 2012

Publikationsdatum:
24. Mai 2012 (online)


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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