Studies towards the total synthesis and structure revision of neaumycin B

Abstract

Neaumycin B is a highly complex natural product that displays a strong synergistic effect with Ramoplanin against methicillin-resistant Staphylococcus aureus (MRSA) and exhibits potent cytotoxic activity against U87 human glioblastoma cells, underscoring its potential for further pharmacological development. However, its structural complexity poses a significant challenge for total synthesis.<br /> The initially proposed structure of Neaumycin B was based on bioinformatic predictions and NMR analysis. Later, total syntheses conducted by different research groups produced identical NMR spectra that did not match the data obtained from the originally isolated compound. This discrepancy led to the conclusion that the original structural assignment was incorrect.<br /> A revised structure was subsequently proposed, involving changes to several stereocenters. Due to the overlap between the commencement of this work and the structure revision, efforts were directed toward synthesizing the C1–C17 fragment in both the originally proposed and the revised stereochemical forms. Additionally, authentic subfragments, such as C1–C9 and C8–C17, were synthesized and compared to previously reported NMR data. The results strongly support the accuracy of the revised structure of Neaumycin B.