Total Synthesis of the Sesquiterpenoid Polyols (±)-Euonyminol and (±)-3,4-Dideoxymaytol, Core Constituents of Esters of theCelastraceae

Abstract

A general synthetic route to the set of polyhydroxylated agarofurans that comprise the core structures of esters present in plants of the Celastraceae family has been devised. The pathway is exemplified with total syntheses of (±)-3,4-dideoxymaytol (3), the nucleus of ever-1 (6), and (±)-euonyminol (4), the sesquiterpenoid core of several cathedulins including K-19 (5). A focal intermediate 19, prepared by Diels−Alder addition of 11 to 12, was identified that permitted stereoselective introduction of an isopropenyl substituent via chelation-controlled, conjugate Grignard addition to give 34. Triflic acid-catalyzed cyclization of 39 afforded the agarofuran skeleton of 3, and subsequent epimerization of the hydroxyl substituent at C1 via a reversible aldol sequence gave 41. Sequential reductions using hydride and catalytic hydrogenation yielded 3 and 4-epi-3,4-dideoxymaytol (51). The route from 19 was extended toward 4 via 56, prepared by directed epoxidation of 34. A trifuoroacetic acid-catalyzed “epoxide-cascade” cyclization of 56 furnished 61, which was advanced to γ-lactone 63 prior to epimerization at C1. Introduction of the 8β hydroxyl function of 69 was followed by an α-ketol transposition to give 71 which was reduced and protected as polysilyl ether 80. Osmylation and replacement of protecting groups produced euonyminol octaacetate 78 which underwent methanolysis to (±)-4.

Catalyzed Asymmetric DielsAlder Reactions of Benzoquinone. Total Synthesis of (−)‐Ibogamine

“…The latter, prepared by oxidation of methyl 2,5-dihydroxybenzoate as reported by Kraus and Taschner [13] and used in situ, was reacted with diene 9 to give cycloadduct 21 in only 36% ee whose absolute configuration was not determined. The racemic version of 21 has provided a convenient platform from which to launch syntheses of polyhydroxylated sesquiterpenoids of the agarofuran family, including (AE)-euonyminol [14], but an efficient asymmetric entry to the highly functionalized decalin core of this group remains elusive at this point. On the other hand, our effort to exploit the catalyzed asymmetric DielsÀAlder reaction of 1,4-benzoquinone in a synthesis of the indole alkaloid (À)-ibogamine (22) was more successful.…”

Structures of New Friedelane-Type Triterpenes and Eudesmane-Type Sesquiterpene and Aldose Reductase Inhibitors from Salacia chinensis

“…The H-H COSY experiment on 5 indicated the presence of three partial structure written in bold lines, as shown in Figure 3. The alkaline hydrolysis of 5 with 5% aqueous potassium hydroxide (KOH) in 1,4-dioxane yielded 3,4-dideoxymaytol (5a), 35 which was also obtained by the alkaline hydrolysis of 9. The positions of three acetyl groups and a benzoyl group in 5 were clarified by HMBC experiment.…”

All-carbon [3 + 2] cycloaddition in natural product synthesis

“…The synthesis of sinensilactam A (20) commenced with a threestep synthesis from ketoeseter 131 to give enone 132 [59] (Scheme 9C). Selective reduction of the ketone moiety of 132 was accomplished under Luche's conditions [65] in the presence of calcium chloride [63] to produce the desired alcohol over three steps. The conversion of 138 to sinensilactam A (20) was achieved in two steps.…”