Recent Advances in the Total Synthesis of Tetramic Acid-Containing Natural Products

Abstract

With incredible bioactivities and fascinating structural complexities, tetramic acid- (TA-) containing natural products have attracted favorable attention among the organic chemistry community. Although the construction of the TA core is usually straightforward, the intricate C3-side chain sometimes asks for some deliberative strategy so as to fulfill an elegant total synthesis. This review mainly covers some exceptional synthetic examples for each type of natural product in recent years, showcasing the great achievements as well as unsettled obstacles in this area, in the hope of accelerating the synthetic and biological investigations for this unique type of natural product.

Total Synthesis of the Potent and Broad-Spectrum Antibiotics Amycolamicin and Kibdelomycin

“…Applying this general plan in the retrosynthesis, 1c was first disconnected to form three fragments of roughly the equal size and complexity (Scheme ): N -glycosyl tetramic acid 2 , trans -decalin 3 , and N -acyl amycolose 4 . We envisioned their recombination through a C -acylation of 2 with 3 and a diastereoselective O -glycosylation of 3 with 4 . , Further, we disconnected 2 through the N -glycosidic bond to the tetramic acid fragment B and the amykitanose C , the latter of which was mapped back to the inexpensive l -rhamnose ( 6 ) by elaborating C1–C4–OH site-selective functionalizations. The decalin fragment A ( 3 ) was anticipated to arise from ester 7 through an Ireland–Claisen rearrangement followed by an RCM reaction.…”

Traceless Solid-Phase Synthesis of Ketones via Acid-Labile Enol Ethers: Application in the Synthesis of Natural Products and Derivatives

“…To demonstrate the practical use of a Wang linker for the traceless synthesis of pharmacologically relevant ketones, we report the synthesis of pyrrolidine-2,4-diones. Pyrrolidine-2,4-dione, the core structure of tetramic acid, was selected as a pharmacologically relevant structure found in natural products [34,35]. Numerous chemical routes for the preparation of tetramic acid and its derivatives have been developed, and the reported syntheses have been reviewed [35,36,37].…”