Total Synthesis of (±)-Illisimonin A, a Neuroprotective Sesquiterpenoid from the Fruits of Illicium simonsii

Abstract

<p>Illisimonin A was isolated from Illicium simonsii and has a previously unreported tricyclic carbon framework. It displayed neuroprotective effects against oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells. It incorporates a highly strained trans-pentalene ring system. We report the first synthesis of illisimonin A. Notable steps in the route include a 1,3-dioxa-2-silacyclohexenetemplated Diels-Alder cycloaddition and type-3 semipinacol rearrangement to generate the trans-pentalene. The final step is an iron-catalyzed C-H oxidation. The synthetic route is robust, with 94 mg prepared in a single pass.</p>

Relative and Absolute Structure Assignments of Alkenes Using Crystalline Osmate Derivatives for X-ray Analysis

“…X-ray structures of crystalline osmate esters have been reported in the literature. Where the organic component was nontrivial, the crystalline osmates were used to elucidate the stereoselectivity of the osmylation reaction, 12,14 the regioselectivity of the reaction, 15 or to help explain the effect of chiral ligands on stoichiometric enantioselective osmylations. 16 Several studies investigating the interactions of OsO 4 with RNA and DNA have produced crystal structures of nucleosideand nucleotide-derived osmates.…”

“…We recently faced the problem of assigning the absolute configuration of the natural product illisimonin A. 12 The synthesis of racemic illisimonin A confirmed the relative configuration of the assigned structure, but an enantioselective route was necessary to determine the absolute configuration. We eventually solved the problem by resolving an alcohol intermediate using (S)-1-(1-naphthyl)ethyl isocyanate and separating the diastereomers by chromatography (Figure 1).…”

“…13 The OsO 4 −TMEDA complex can be directed by hydrogen bonding and frequently reacts with good diastereoselectivity. 12 The resulting osmate esters were remarkably stable, and Donohoe determined the structures of a few of the products by crystallography. 12 With little to lose and still uncertain of the outcome with crystals of 3, we osmylated the alcohol derived from carbamate 1.…”

“…12 The resulting osmate esters were remarkably stable, and Donohoe determined the structures of a few of the products by crystallography. 12 With little to lose and still uncertain of the outcome with crystals of 3, we osmylated the alcohol derived from carbamate 1. This experiment directly led to a crystalline derivative 4. contained both a TBS and a BOM group, which often limit crystallinity, and yet it formed X-ray-quality crystals.…”

Synthesis of a Bicyclo[2.2.1]heptane Skeleton with Two Oxy-Functionalized Bridgehead Carbons via the Diels–Alder Reaction

“…Their group also developed this methodology for natural product synthesis. 11 On the contrary, the DA reaction using a cyclopentadiene compound, where the two oxy functions are located at positions C-1 and C-4, is expected to provide bicyclo[2.2.1]heptane compounds with two oxy-functionalized bridgehead carbons. Such compounds can be considered as versatile building blocks for synthesizing complex carbocyclic compounds via a skeletal rearrangement 12 or C−C fragmentation 13 assisted by an oxy-functionalized The synthetic strategy is illustrated in Scheme 2.…”