Nature-Inspired Total Synthesis of (−)-Fusarisetin A

Abstract

A concise, protecting group-free total synthesis of (−)-fusarisetin A (1) was efficiently achieved in 9 steps from commercially available (S)-(−)-citronellal. The synthetic approach was inspired by our proposed biosynthesis of 1. Key transformations of our strategy include a facile construction of the decalin moiety that sets the stage for a stereoselective IMDA reaction and a one-pot TEMPO induced radical cyclization/aminolysis that forms the C ring of 1. Our route is amenable to analogue synthesis for biological evaluation.

A new enzyme involved in the control of the stereochemistry in the decalin formation during equisetin biosynthesis

“…Fusarisetin A (2), which was isolated as an acinar morphogenesis inhibitor, possesses a unique pentacyclic ring system [10] and has been proposed to be converted from 1, since 2 contains the basic skeleton of 1 [11]. To establish the biosynthetic pathway for 2, we conducted the genome mining of Fusarium sp.…”

Asymmetric Synthesis and Biosynthetic Implications of (+)‐Fusarisetin A

“…[7] Theodorakis and co-workers later proposed 3 to be the biosynthetic precursor of 1 and accomplished a biomimetic synthesis of (À)-1. [8] Equisetin (3) is another secondary metabolite isolated from Fusarium sp. and contains the basic skeleton (A,B, and E rings) of (+)-1 but is at a lower oxidation state.…”

Asymmetric synthesis of dihydroartemisinic acid through intramolecular Stetter reaction

“…8 We have prepared compound 8 from (R)-(+)-citronellal via a Ru-catalyzed Eselective olefin cross-metathesis (CM) with ethyl methacrylate in 70% yield using G-II catalyst in single step (Scheme 2). 9 With the required α,β-unsaturated ester (8) in our hand, the model version of intramolecular Stetter reaction 10 was attempted with the thiazolium catalyst in anhydrous toluene as a solvent as reported by Trost and co-workers for their synthesis of hirsutic acid. 11 To our delight, the reaction proceeded smoothly and furnished compound 9 with overall good diastereoselectivity (12:1) in favour of the conformationally more favourable diastereomer (desired one for our synthetic exercise).…”