Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
The Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02142, USA.
Science. 2022 Feb 25;375(6583):894-899. doi: 10.1126/science.abm6509. Epub 2022 Feb 24.
The natural product himastatin has an unusual homodimeric structure that presents a substantial synthetic challenge. We report the concise total synthesis of himastatin from readily accessible precursors, incorporating a final-stage dimerization strategy that was inspired by a detailed consideration of the compound's biogenesis. Combining this approach with a modular synthesis enabled expedient access to more than a dozen designed derivatives of himastatin, including synthetic probes that provide insight into its antibiotic activity.
天然产物海兔素具有不寻常的同源二聚体结构，这给其合成带来了巨大的挑战。我们报道了海兔素的简洁全合成，该合成从易得的前体出发，采用最终阶段的二聚化策略，该策略受到了对该化合物生物合成的详细考虑的启发。将这种方法与模块化合成相结合，使我们能够快速获得十几种设计的海兔素衍生物，包括提供其抗生素活性见解的合成探针。
