A Short Access to the Skeleton of Elisabethin A and Formal Syntheses of Elisapterosin B and Colombiasin A

Abstract

A short stereoselective synthesis of the Elisabethin A skeleton 4 is described, which opens a formal access to the diterpenes Elisapterosin B and Colombiasin A as well. Key reactions were an intermolecular endo-selective Diels-Alder reaction to generate the decalin part of the molecule, a chemo- and diastereoselective allylation of an aldehyde with allylzinc, a palladium ene annulation of the cyclopentane ring, and a novel sulfonium ylide induced fragmentation of a polycyclic ketone. Additional insights have been gained for the crucial epimerization at C-2.

Broadly Applicable Stereoselective Syntheses of Serrulatane, Amphilectane Diterpenes, and Their Diastereoisomeric Congeners Using Asymmetric Hydrovinylation for Absolute Stereochemical Control

“…For example, we find that 36a is readily oxidized to a quinone-alcohol 43a in modest yield (68%) upon brief exposure to ceric ammonium nitrate in aqueous acetonitrile. The structure of 43a was confirmed by comparison of 1 H and 13 C NMR spectrum with a racemic variant of this compound that has been prepared by Mulzer 38 in 10 steps from 2,5-dihydroxy-4-methoxy-3-methylbenzaldehyde in ~22% yield. The corresponding tri- i- propylsilylether 43b has been converted into colombiasin ( 12 ) and elisapterosin ( 13 ) by Rychnovsky 39 , thus establishing formal syntheses of these two natural products.…”

“…24a,38,48 The allyl alcohol 38 (Scheme 11), which was prepared as an intermediate for nor- elisabethadione, appeared to be an attractive precursor for this compound. We have explored the chemistry of this intermediate in an attempt to synthesize the core skeleton of elisabethin A via a spiroannulation shown in Scheme 19.…”

“…Elisabethin A (Figure ), a possible biogenetic precursor of colombiasin and elisapterosin, remains an elusive molecule despite several efforts to synthesize this compound. ,, The allyl alcohol 38 (Scheme ), which was prepared as an intermediate for nor- elisabetha­dione, appeared to be an attractive precursor for this compound. We have explored the chemistry of this intermediate in an attempt to synthesize the core skeleton of elisabethin A via a spiroannulation shown in Scheme .…”

Efforts toward the Total Synthesis of Elisabethin A

“…9,10 In 2014, Mulzer et al reported a second approach to elisabethin A (1) but was not able to prove their claims made in 2003. 11 Herein, we wish to report two different approaches toward the total synthesis of elisabethin A (1). Both were running in parallel with the idea to push forward with the most promising approach to completion.…”

Synthesis of Spirocyclohexadienones through Radical Cascade Reactions Featuring 3-Fold Carbon–Carbon Bond Formation

“…From such starting materials, spirocyclization can be achieved under transition metal catalysis using palladium, iridium, or gold catalysts (Scheme , reaction 1). , Alternatively, the triple bond may be attacked by electrophilic reagents such as iodine monochloride or N -bromo succinimde to trigger the cyclization onto the electron-rich aromatic system (Scheme , reaction 2). , Complementary nucleophilic ipso cyclizations on electron-poor aromatic systems have also been reported . Radical induced spirocyclizations of aryl alkynes have so far been conducted with carbon-, sulfur-, and phosphorus-centered radicals (Scheme , reaction 3). − …”