Synthesis of Cytospolide Analogues and Late-State Diversification Thereof

The cytospolides are a novel group of fungal secondary metabolites first described in 2011. Although all 17 natural derivatives share the same C-14 polyketide backbone, they exhibit a fairly broad structural diversity regarding their oxygenation and acetylation pattern as well as macrolide structure...

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Bibliographic Details
Published in:Journal of organic chemistry 2019-03, Vol.84 (6), p.3132-3147
Main Authors: Ehrlich, Gunnar, Stark, Christian B. W
Format: Article
Language:English
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Summary:The cytospolides are a novel group of fungal secondary metabolites first described in 2011. Although all 17 natural derivatives share the same C-14 polyketide backbone, they exhibit a fairly broad structural diversity regarding their oxygenation and acetylation pattern as well as macrolide structure, e.g., monocyclic nonanolide core or bicyclic ring systems with a bridging THF ring. In the present work, the prospects for an extension of the structural diversity of cytospolides have been investigated. On the basis of a previously established synthesis of cytospolide D, a modified route to a truncated analogue carrying an alkyne instead of the natural n-pentyl side chain has been developed. In a bioinspired approach the so-derived cytospolide D alkyne analogue has been further converted to bicyclic and THF ring containing derivatives with a different backbone architecture. Finally, Sonogashira couplings or Huisgen–Sharpless click reactions have been used for late-stage diversifications. Thus, a set of 15 novel and structurally diverse natural product derivatives has been synthesized in a highly efficient manner.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.8b02999