Biomimetic Total Synthesis and Investigation of the Non-Enzymatic Chemistry of Oxazinin A.
Angew Chem Int Ed Engl
; 61(38): e202208029, 2022 09 19.
Article
em En
| MEDLINE
| ID: mdl-35881566
ABSTRACT
We report the first total synthesis of an antimycobacterial natural product oxazinin A that takes advantage of a multi-component cascade reaction of anthranilic acid and a precursor polyketide containing an aldehyde. The route utilized for the synthesis of the pseudodimeric oxazinin A validates a previously proposed biosynthetic mechanism, invoking a non-enzymatic pathway to the complex molecule. We found a 76 10 9 5 ratio of oxazinin diastereomers from the synthetic cascade, which is an identical match to that found in the fermentation media from the fungus Eurotiomycetes 110162. Further investigation of the non-enzymatic formation of oxazinin A using 1 H-15 N HMBC NMR spectroscopy allowed for a plausible determination of the stepwise mechanism. The developed route is highly amenable for the synthesis of diverse sets of analogs around the oxazinin scaffold to study structure-activity relationships (SAR).
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Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
Biomimética
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos