Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins Allowing a Formal Synthesis of Trichoderone A

Abstract

Aspochalasins are leucine-derived cytochalasins. Their complexity is often associated to a high degree of biosynthetic oxidative transformations that could inspire a two-phase strategy in total synthesis. In that context, we describe the synthesis of a putative biomimetic tetracyclic intermediate. The key constructive steps are an intramolecular Diels-Alder reaction to install the characteristic isoindolone core of cytochalasins, whose branched precursor was obtained from a stereoselective Ireland-Claisen rearrangement made on a highly unsaturated substrate. This work also constitutes a formal synthesis of trichoderone A.

Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins and Formal Synthesis of Trichoderone A

“…In conclusion, we were able to perform the synthesis of a key synthetic precursor (5) of tetracyclic aspochalasan natural products and derivatives, the structure of which could be confirmed by X-ray analysis of an epoxide product (26). 40 Compound 5 constitutes a good entry to perform the "oxidase" phase in the bio-inspired synthesis of natural products such as trichoderone A (3) and trichodermone (4). In particular, this work constitutes a formal synthesis of 3.…”