(−)-Lomaiviticin A (4) is a complex C₂-symmetric bacterial metabolite that contains two diazofluorene functional groups. The diazofluorene consists of naphthoquinone, cyclopentadiene, and diazo substituents fused through a σ- and π-bonding network. Additionally, (−)-lomaiviticin A (4) is a potent cytotoxin, with half-maximal inhibitory potency (IC₅₀) values in the low nanomolar range against many cancer cell lines. Because of limitations in supply, its mechanism of action had remained a “black box” since its isolation in the early 2000s. In this Account, I describe how studies directed toward the total synthesis of (−)-lomaiviticin A (4) provided a platform to elucidate the emergent properties of this metabolite and thereby connect chemical reactivity with cellular phenotype.

中文翻译：

---

（-）-Lomaiviticin A的作用机理

（-）-Lomaiviticin A（4）是一个复杂的C ₂对称细菌代谢产物，包含两个重氮芴官能团。重氮芴由萘醌，环戊二烯和通过σ和π键网络稠合的重氮取代基组成。另外，（-）-lomaiviticin A（4）是一种有效的细胞毒素，对许多癌细胞系的抑制作用（IC ₅₀）值在低纳摩尔浓度范围内为一半。由于供应方面的限制，自2000年代初孤立以来，其行动机制一直是一个“黑匣子”。在本报告中，我描述了如何针对（-）-lomaiviticin A（4的全部合成）进行研究。）提供了一个平台，以阐明这种代谢物的新兴特性，从而将化学反应性与细胞表型联系起来。