Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence

Zhiqiang Ma, Xiaolei Wang, Xiao Wang, Rodrigo A. Rodriguez, Curtis E. Moore, Shuanhu Gao, Xianghui Tan, Yuyong Ma, Arnold L. Rheingold, Phil S. Baran, Chuo Chen

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Abstract

Cycloaddition is an essential tool in chemical synthesis. Instead of using light or heat as a driving force, marine sponges promote cycloaddition with a more versatile but poorly understood mechanism in producing pyrrole-imidazole alkaloids sceptrin, massadine, and ageliferin. Through de novo synthesis of sceptrin and massadine, we show that sponges may use single-electron oxidation as a central mechanism to promote three different types of cycloaddition. Additionally, we provide surprising evidence that, in contrast to previous reports, sceptrin, massadine, and ageliferin have mismatched chirality. Therefore, massadine cannot be an oxidative rearrangement product of sceptrin or ageliferin, as is commonly believed. Taken together, our results demonstrate unconventional chemical approaches to achieving cycloaddition reactions in synthesis and uncover enantiodivergence as a new biosynthetic paradigm for natural products.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalScience
Volume346
Issue number6206
DOIs
StatePublished - Oct 10 2014

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Cite this

Ma, Z., Wang, X., Wang, X., Rodriguez, R. A., Moore, C. E., Gao, S., Tan, X., Ma, Y., Rheingold, A. L., Baran, P. S., & Chen, C. (2014). Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence. Science, 346(6206), 219-224. https://doi.org/10.1126/science.1255677