A unified strategy to ent-kauranoid natural products : total syntheses of (–)-maoecrystal Z, (–)-trichorabdal A, and (–)-longikaurin E


Autoria(s): Yeoman, John Thomas Schafer
Data(s)

2014

Resumo

<p>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.</p> <p>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<sup>(II)</sup>-mediated reductive cascade cyclization, which forms two rings and establishes four new stereocenters in a single step, and a Ti<sup>(III)</sup>-mediated reductive epoxide-acrylate coupling that yields a functionalized spirolactone product, which forms a core bicycle of maoecrystal Z.</p> <p>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.</p>

Formato

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Identificador

http://thesis.library.caltech.edu/8170/44/Yeoman-John-2014-FullThesis-Final.pdf

http://thesis.library.caltech.edu/8170/1/Yeoman-John-2014-Title-TOC.pdf

http://thesis.library.caltech.edu/8170/7/Yeoman-John-2014-Ch1.pdf

http://thesis.library.caltech.edu/8170/13/Yeoman-John-2014-Ch2.pdf

http://thesis.library.caltech.edu/8170/19/Yeoman-John-2014-App1.pdf

http://thesis.library.caltech.edu/8170/25/Yeoman-John-2014-App2.pdf

http://thesis.library.caltech.edu/8170/31/Yeoman-John-2014-Ch3.pdf

http://thesis.library.caltech.edu/8170/37/Yeoman-John-2014-App3.pdf

http://thesis.library.caltech.edu/8170/43/Yeoman-John-2014-About-Author.pdf

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. http://resolver.caltech.edu/CaltechTHESIS:03252014-222127174 <http://resolver.caltech.edu/CaltechTHESIS:03252014-222127174>

Relação

http://resolver.caltech.edu/CaltechTHESIS:03252014-222127174

http://thesis.library.caltech.edu/8170/

Tipo

Thesis

NonPeerReviewed