A Unified Strategy to Ent-Kauranoid Natural Products: Total Syntheses of (-)-Maoecrystal Z, (-)-Trichorabdal A, and (-)-Longikaurin E

Citation

Yeoman, John Thomas Schafer (2014) A Unified Strategy to Ent-Kauranoid Natural Products: Total Syntheses of (-)-Maoecrystal Z, (-)-Trichorabdal A, and (-)-Longikaurin E. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/5TDN-7M11. https://resolver.caltech.edu/CaltechTHESIS:03252014-222127174

Abstract

The diterpenoid constituents of the Isodon plants have attracted reasearchers interested in both their chemical structures and biological properties for more than a half-century. In recent years, the isolations of new members displaying previously unprecedented ring systems and highly selective biological properties have piqued interest from the synthetic community in this class of natural products.

Reported herein is the first total synthesis of such a recently isolated diterpenoid, (–)-maoecrystal Z. The principal transformations implemented in this synthesis include two highly diastereoselective radical cyclization reactions: a Sm^(II)-mediated reductive cascade cyclization, which forms two rings and establishes four new stereocenters in a single step, and a Ti^(III)-mediated reductive epoxide-acrylate coupling that yields a functionalized spirolactone product, which forms a core bicycle of maoecrystal Z.

The preparation of two additional ent-kauranoid natural products, (–)-trichorabdal A and (–)-longikaurin E, is also described from a derivative of this key spirolactone. These syntheses are additionally enabled by the palladium-mediated oxidative cyclization reaction of a silyl ketene acetal precursor that is used to install the bridgehead all-carbon quaternary stereocenter and bicyclo[3.2.1]octane present in each natural product. These studies have established a synthetic relationship among three architecturally distinct ent-kaurane diterpenoids and have forged a path for the preparation of interesting unnatural ent-kauranoid structural analogs for more thorough biological study.

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