Miniaturized Cultivation Profiling (MATRIX)-Facilitated Discovery of Noonazines A-C and Noonaphilone A from an Australian Marine-Derived Fungus, CMB-M0339.

Subjecting the Australian marine-derived fungus CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (-), along with the known analogue coelomycin (), as well as a new azaphilone, noonaphilone A (). Structures were assigned to - on the basis of a detailed spectroscopic analysis, and in the case of -, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for -, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, incorporates a rare -Tyr motif, typically only reported in a limited array of metabolites. Similarly, a plausible biosynthetic pathway is proposed for , highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7 noonaphilone A () versus the 7 deflectin 1a ().