Seven-Step Total Synthesis of Sporothriolide

Abstract

An enantioselective total synthesis of sporothriolide, a bioactive furofurandione-type fungal metabolite, has been achieved in a 21% overall yield from a commercially available β,γ-unsaturated carboxylic acid via seven steps. The key steps of this synthesis include a highly diastereoselective Michael addition of a chiral oxazolidinone derivative to a nitro olefin, the exploitation of an aromatic ring as a masked carboxylic acid functionality, and the base-promoted elimination of nitrous acid to install the α-methylene lactone unit of sporothriolide in the final step.

Biomimetic-inspired synthesis of sporochartines through Diels–Alder reaction between enantiopure (−)-sporothriolide and (+)-trienylfuranol A

“…A21, an endophytic fungus in the leaves of Ginkgo biloba . 6 Racemic 7 and enantioselective 8 syntheses of sporothriolide 3 have been performed and its biosynthetic pathway was fully identified. 9…”

Chiral Cyclopropenimine‐catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,β‐Unsaturated Isoxazoles

“…The asymmetric Michael additions can be realized by various chiral metal-or organo-catalysts to provide Michael adducts in high yields and enantioselectivities. [1][2][3] With the Renaissance of organocatalysis, [4][5][6][7] many chiral organocatalysts have been discovered to inspire different activation modes in organic synthesis. Among them, chiral Brønsted acids, chiral hydrogenbonding catalysts, and chiral bifunctional amines are very attractive for their structural diversity and high efficiency in catalytic asymmetric synthesis.…”

“…The asymmetric Michael addition is regarded as a very important reaction for chiral C−C and C−X (X is heteroatom) bond formations in modern organic synthesis. The asymmetric Michael additions can be realized by various chiral metal‐ or organo‐ catalysts to provide Michael adducts in high yields and enantioselectivities [1–3] . With the Renaissance of organocatalysis, [4–7] many chiral organocatalysts have been discovered to inspire different activation modes in organic synthesis.…”

Triethylamine-Promoted Henry Reaction/Elimination of HNO2/Cyclization Sequence of Functionalized Nitroalkanes and 2-Oxoaldehydes: Diversity-Oriented Synthesis of Oxacycles

“…Among the developed preparation methods, the Michael addition of nitroalkanes to corresponding acceptors bearing ester or ketone moieties provided a straightforward procedure for the construction of β-nitro esters and ketones (Scheme a) . However, despite numerous efforts, the use of this elimination strategy remains a vastly underutilized protocol; most reported examples focused only on the construction of electron-deficient alkene moieties, while the use of in situ-formed nitro precursors from readily available nitroalkanes to produce more complex architectures has been much less explored . Therefore, the development of new strategies to embed elimination of HNO 2 into a cascade process that yield biologically important and synthetically useful products is a highly desirable but challenging subject.…”