Recent Advances in the Total Synthesis of Natural Products Containing Eight-Membered Carbocycles (2009–2019)

Abstract

Natural products containing eight-membered carbocycles constitute a class of structurally intriguing and biologically important molecules such as the famous diterpenes taxol and vinigrol. Such natural products are being increasingly investigated because of their fascinating architectural features and potent medicinal properties. However, synthesis of natural products with cyclooctane moieties has proved to be highly challenging. This review highlights the recently completed total syntheses of natural products with eight-membered carbocycles with a focus on strategic considerations. A collection of 27 representative studies from the literature covering the decade from 2009 to 2019 is described in chronological order with relevant studies grouped together, including syntheses of the same natural product by different research groups using different strategies. Finally, a summary and outlook including a discussion of the major features of each strategy used in the syntheses are presented. This review illustrates the diversity and creativity in the elegant synthetic designs of eight-membered carbocycles. We hope this review will provide timely illumination and beneficial guidance for future synthetic efforts for organic chemists who are interested in this area.

Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

“…The reaction proceeds chemoselectively, regioselectively, and diastereoselectively, thus establishing a new and relatively general strategy for the efficient and straightforward synthesis of various functionalized and synthetically challenging bridged medium-sized ring systems (e.g., bicyclo[5.2.2], bicyclo[4.2.2], azabicyclo[4.2.2], bicyclo[3.2.2], azabicyclo[3.2.2], and oxabicyclo[3.2.2] ring systems). Particularly, this work represents, to our knowledge, the first example of a rhodium-catalyzed intramolecular (3+2) cycloaddition to make synthetically challenging eight-membered ring systems 53 and represents the first example of an intramolecular dipolar cycloaddition for constructing all-carbon bicyclo[m.2.2] ring systems. To the best of our knowledge, the first asymmetric total synthesis of nakafuran-8 was achieved using this method.…”

Structural basis of the membrane intramolecular transacylase reaction responsible for lyso-form lipoprotein synthesis

“…4 ). Different sized rings are characterised by different strain energies 46 . That for a nine-membered ring, at least in the case of cycloalkanes, is strained to the extent of 2–3 kcal/mol more than its eight-membered counterpart.…”

The Total Synthesis of Diquinane‐Containing Natural Products

“…In the context of total synthesis, to access one particular substructure, multifarious synthetic inspirations may come out andw ork out as practical strategies. In reality,i ti st rue that somec ommon subunits embedded in complex natural products have generally resulted in av ariety of synthetic strat-egies, such as cyclopropane, [6] cyclobutane, [7] eight-membered rings, [8] anda ll-carbon quaternary stereocenters. [9] Therefore, it is of great significance and high interest to summarize and analyze those achievements in the literaturep ertaining to the same structural feature.…”