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Isobenzofurans as Synthetic Intermediates: Synthesis and Biological Activity of 8‐ epi ‐(–)‐Ajudazol B
Author(s) -
Adair Liam,
Egan Ben A.,
Pearson Colin M.,
LopezGonzalez Ricardo,
Kuchar Michal,
MendozaMendoza Artemio,
Prunet Joëlle,
Marquez Rodolfo
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001216
Subject(s) - chemistry , polyketide , botrytis cinerea , antifungal , stereochemistry , biological activity , alkylation , dimethyldioxirane , total synthesis , convergent synthesis , metabolite , chemical synthesis , combinatorial chemistry , biosynthesis , biochemistry , organic chemistry , in vitro , enzyme , microbiology and biotechnology , archaeology , biology , history , catalysis
Ajudazol B is a polyketide secondary metabolite, isolated from the myxobacterium Chondromyces crocatus , that exhibits potent biological activity. Herein, we report a convergent total synthesis of 8‐ epi ‐(–)‐ajudazol B. The key step is a regio‐selective alkylation and oxidative rearrangement of a reactive isobenzofuran intermediate that generates the isochromanone core. This approach provides a fast and efficient method to synthesise analogues of ajudazol B from simple aldehydes, allowing assessment of structure‐activity relationships. The antifungal activity of 8‐ epi ‐(–)‐ajudazol B as well as that of related analogues has been assessed using Botrytis cinerea . The results indicate that the isochromanone unit is key for antifungal activity.