Exploring the Nonenzymatic Origin of Duclauxin-like Natural Products.

Chemical-biological efforts to increase the diversity of duclauxin ( 1 )-like molecules for medicinal chemistry purposes unveiled the reactivity of duclauxin ( 1 ) toward amines and alcohols. To expand the compound class, a semisynthetic strategy conjugating amines to duclauxin ( 1 ) was employed. Insights gained from this approach led to the hypothesis that certain duclauxin-like "natural products" such as talaromycesone B ( 2 ), bacillisporin G ( 3 ), xenoclauxin ( 4 ), bacillisporins F ( 5 / 6 ), bacillisporins J ( 8 / 9 ), bacillisporins I ( 12 / 13 ), and verruculosin A ( 38 ) may be isolation artifacts rather than enzymatic products. Further experimentation, involving adsorption of 1 onto silica gel, resulted in the production of 2 - 6 . To gain insights into the conditions that generate such molecules, one-step reactions under mild conditions were set. Outcomes from both experiments confirmed that duclauxin-like molecules are generated via nonenzymatic reactions. This article presents analytical evidence, indicating that these molecules originate from 1 , with the epimeric mixture of bacillisporins J ( 8 and 9 ) acting as the primary intermediate.