Biomimetic Total Synthesis and Investigation of the Non‐Enzymatic Chemistry of Oxazinin A

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