Toward a General Route to the Eunicellin Diterpenes:  The Asymmetric Total Synthesis of Deacetoxyalcyonin Acetate

Abstract

A novel approach to the hydroisobenzofuran core utilizing a TiCl4-mediated [4+3] annulation is reported. This [4+3] annulation protocol provides a short, general route to the hydroisobenzofuran core present in the eunicellin diterpenes. Using this annulation, a short synthesis (17 steps) of deacetoxyalcyonin acetate, a member of the eunicellin family, has been achieved.

Photochemische Reaktionen als Schlüsselschritte in der Naturstoffsynthese

“…Das aus a-Phellandren leicht erhältliche Cyclobutanon 101 ergab so bei Bestrahlung mit einer Hg-Mitteldrucklampe das gemischte Bisacetal 102, das als Intermediat in der Synthese des (À)-Deacetoxyalcyoninacetats (103), eines Eunicellinditerpens, diente (Schema 29). [151] Die Bildung der Oxacarbene verläuft als Singulettreaktion stets, so auch im vorliegenden Fall, unter Retention der Konfiguration an der gespaltenen Bindung. Weitere Anwendungen dieser Umlagerung finden sich in den Synthesen des (AE )-Prostaglandin-F 2a [152] und der Pilzinhaltsstoffe (AE )-Muscarin [153] und (AE )-allo-Muscarin.…”

The bio-based methyl coumalate involved Morita–Baylis–Hillman reaction

“…6a contains the hydro-isobenzofuran core, which can be found in many bioactive natural products. [50][51][52][53] Similarly, 6b…”

Efficient Total Synthesis of Bioactive Natural Products: A Personal Record

“…Using a similar strategy for the introduction of the A/B ring system prior to construction of the medium‐sized C ring, Campbell and Johnson applied a Lewis acid catalyzed [3 + 2] cycloaddition reaction to provide stereoselective access to the A/B ring fragment in their total synthesis of (+)‐polyanthellin A [52]. In contrast, Molander et al [53]. completed the total synthesis of deacetoxyalcyonin acetate via the photochemical rearrangement of a cyclobutanone.…”