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

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

Key words

ansamitocins - antitumor agents - biosynthesis - muta­synthesis - semisynthesis

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