Multiply Unsaturated and ω‐Brominated β‐Ketothioesters for Synthesizing β‐Ketolactams and the Scaffolds of Fully Enolized N‐Hydroxy‐3‐(polyenoyl)pyridine‐2,4‐dione Natural Products

Abstract

AbstractFully enolized N‐hydroxypyridine‐2,4‐diones with a 3‐enoyl or 3‐dienoyl or 3‐trienoyl substituent (collectively named “3‐polyenoyl substituent“ hereafter) define the core of a number of δ‐lactam natural products. We developed a strategy for establishing such motifs in a convergent and stereoselective manner. The polyenoyl moiety of our target molecules stemmed from simply, two‐fold or three‐fold unsaturated and almost completely enolized ω‐bromo‐β‐ketothioesters, two of which were obtained for the first time. The N‐bound hydroxy group of our target structures originated from an O‐(2,4,6‐trimethoxybenzyl)‐protected β‐(hydroxylamino)propionic ester, first obtained in this study, too. The mentioned building blocks were combined intermolecularly by a thioester hydroxylaminolysis and thereafter intramolecularly by a Williams‐type Dieckmann cyclization. The resulting N‐(2,4,6‐trimethoxybenzyloxy)dihydropyridine‐2,4‐diones were oxidized with CBrCl3 and DBU. The N‐(2,4,6‐trimethoxybenzyloxy)pyridine‐2,4‐diones gained thereby were debenzylated – jointly with their (4‐methoxybenzyl) aryl ether moiety – with F3CCO2H. This liberated the target structures.