A Modular Approach to Angularly Fused Polyquinanes via Ring-Rearrangement Metathesis: Synthetic Access to Cameroonanol Analogues and the Basic Core of Subergorgic Acid and Crinipellin.

Abstract

We describe a modular approach to angularly fused polyquinanes that are core units of many natural products such as cameroonanol, subergorgic acid, and crinepellin, etc. in excellent yields by employing atom-economic ring-rearrangement metathesis as a key step. Our work highlights, the synthesis of cameroonanol analogues 1-6 and their ester derivatives by using the stereoselective reduction of the carbonyl group by using DIBAL-H- and DCC-mediated coupling as the key reactions. The subergorgic acid core 7 was produced by LDA-mediated kinetically controlled regio- and stereoselective ring-junction allylation as a critical step. Moreover, it is worth mentioning that the present strategy relies on a less explored exo-dicyclopentadiene-1-one (8) and produces highly congested polycyclic frameworks containing up to seven contiguous stereogenic centers including quaternary carbons up to two. All of the new molecules were characterized by NMR data. The structure and relative stereochemistry of some compounds were confirmed by chemical methods and further supported by single-crystal X-ray diffraction studies. The newly reported tri- and tetraquinane skeletons are present in many naturally occurring bioactive polyquinanes. Hence, this strategy is useful for designing various "druglike molecules" and expands the chemical space of cyclopentanoids that are useful in medicinal chemistry.