American Chemical Society
jo9b00961_si_001.pdf (21.04 MB)

Biomimetic Synthesis of Mitchellenes B–H from the Abundant Biological Precursor 14-Hydroxy-6,12-muuroloadien-15-oic Acid

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journal contribution
posted on 2019-07-24, 14:12 authored by Julian Klepp, Nicholas J. Sadgrove, Sarah V. A.-M. Legendre, Christopher J. Sumby, Ben W. Greatrex
A step-economic biomimetic synthesis of mitchellenes B–H found in Eremophila sturtii has been achieved. Starting from the putative muurolane biological precursor, redox isomerization of the allylic alcohol gave an epimeric mixture of aldehydes, which could be used as a handle for cyclization onto the C6 position, using Bu3SnH-mediated radical cyclization or NHC-catalyzed Stetter reaction. The NHC-mediated approach was superior as the epimeric mixture underwent a dynamic kinetic resolution during the reaction, and reduction of the mixture with NaBH4 selectively formed the mitchellene ring system in 56% yield for the three steps. In the campaign to obtain the acid-starting material, two new natural products, mitchellene H and a muurolane aldehyde, were isolated. Synthetic procedures to access this family of natural products will enable further studies on their biological properties.