Elisabethin A: A Marine Diterpenoid Yet To Surrender to Total Synthesis

Abstract

Mysterious and elusive, elisabethin A (1, pictured with the West Indian sea whip Pseudopterogorgia elisabethae from which it was isolated), has not yet succumbed to total synthesis—or has it? Two recent attempts at the synthesis of this challenging target are examined, but questions still remain as to the absolute configuration of the natural product and the synthetic material.

Efficient and Green Telescoped Process to 2-Methoxy-3-methyl-[1,4]benzoquinone

“…The nitric acid oxidation of phenols into the corresponding [1,4]benzoquinones has been known for a century. Nakao and co-workers 14 used such a protocol in the synthesis of antileukemic agents on the basis of 2,5-disubstituted [1,4]benzoquinones, and such a protocol was used by Cohen and co-workers 15 in a total synthesis of vitamin E (tocopherol), but the nitric acid oxidation protocol has to the best of our knowledge never been reported for the preparation of the title compound 3.…”

“…Methoxy-and methyl-substituted [1,4]benzoquinone and phenolic derivatives constitute important classes of building blocks because such moieties are found in a wide range of biologically active compounds. Thus, they are essential basic building blocks for natural product synthesis.…”

“…However, the synthetic chemist often ignores the challenge related to the synthesis of the basic starting compounds, which very often thus results in synthetic paths involving environmentally atrocious and noxious reagents. For example, Cr VI salts (dichromate) have for years been known to be carcinogenic; nevertheless, they are still utilized for oxidation purposes in organic synthesis and are frequently employed in reaction protocols for the preparation of [1,4]benzoquinone derivatives. The popularity of the dichromate protocol for the preparation of benzoquinones is probably a result of the high selectivity and yield that in general is achieved.…”

“…The popularity of the dichromate protocol for the preparation of benzoquinones is probably a result of the high selectivity and yield that in general is achieved. A protocol disclosed by Vliet 9 more than 70 years ago gently provides [1,4]benzoquinone from hydro-quinone with high selectivity and yield (86-92%). Other lengthy protocols involving cerium diammonium hexanitrate 10 as the oxidant were also disclosed for the purpose of preparing [1,4]benzoquinone derivatives.…”

Benzothiazines in Organic Synthesis. Stereoselectivity in the Intermolecular Michael Addition Reactions of Benzothiazines

“…At the outset of our work, no synthesis of 2 existed. Mulzer and co-workers reported a synthesis of 2 , but the accuracy of this report has been challenged …”