Total Synthesis of Norsampsones A and B, Garcinielliptones N and O, and Hyperscabrin A

Abstract

The asymmetric total synthesis of five decarbonyl polycyclic polyprenylated acylphloroglucinols norsampsnes A (3) and B (4), garcinielliptones O (5) and N (6), and hyperscabrin A ( 7) is described. The synthesis to construct the core substituted cyclohexanone ring of these natural products was achieved by a key Dieckmann condensation. The chirality of the molecules was introduced by the stereoselective alkylation with Evans' oxazolidinones. The synthesis could be run on grams scale, and the Dieckmann condensation was investigated through the DFT calculations to help improve the yield of garcinielliptone O (5). Determination of the absolute configuration of garcinielliptones O (5) and N (6) was also achieved.

Sequential Dieckmann cyclization enables the total synthesis of 7-epi-clusianone and 18-hydroxy-7-epi-clusianone

“…To our delight, the Dieckmann reaction proceeded smoothly and afforded the annulated products 16a and 16b as single diastereomers in high yields. Based on the results and our previous finding, 44 a possible transition state involved in the Dieckmann reaction is illustrated in Scheme 4. This indicated that the ester group was preferred to be at the equatorial position.…”

“…Having acquired the crucial linear precursors 7 , we reached the stage for the key Dieckmann reaction to construct the first six-membered ring of the bicyclic core of PPAPs (Scheme 4). Based on our previously reported protocol for the synthesis of decarbonylated polycyclic polyprenylated acylphloroglucinols, 44 we subjected the linear precursors 7 to t -BuOK in THF at 0 °C. To our delight, the Dieckmann reaction proceeded smoothly and afforded the annulated products 16a and 16b as single diastereomers in high yields.…”

Norascyronones A and B, 2,3,4-nor-Polycyclic Polyprenylated Acylphloroglucinols from Hypericum ascyron

“…Polycyclic polyprenylated acylphloroglucinols (PPAPs), possessing highly oxygenated acylphloroglucinol cores densely substituted by prenyl or geranyl side chains, are a group of structurally fascinating and synthetically challenging natural products that collectively exhibit a broad range of biological activities. , Up to date, more than 540 PPAPs were reported exclusively from the plant of families Hypericaceae and Clusiaceae , , of which the majority is bicyclic polyprenylated acylphloroglucinols (BPAPs) featuring a bicyclo[3.3.1]­nonane-2,4,9-trione core, as exemplified by hyperforin and garcinol. , Biosynthetically, BPAPs may not only further cyclize to caged PPAPs with the adamantane or homoadamantane skeleton but also be oxidized to open the ring to generate seco -BPAPs, such as hyphenrone A. , Besides, a small class of structurally related natural products with a simpler cyclohexanone core, − nor -BPAP derivatives, were considered to be derived from BPAPs via degradation of C-2, C-2/3, or C-2/3/4 (together with the C-3 side chain), respectively. According to a literature survey, a total of 18 nor -BPAPs with such architecture have been reported. − As a part of our systematic search for bioactive PPAPs from Hypericum plants, ,− the chemical constituents of Hypericum ascyron ,− were further investigated, and three new nor -BPAP derivatives, norascyronones A–C ( 1 – 3 ), were characterized (Figure ). Interestingly, compounds 1 and 2 sharing an intriguing 6/6/5/6 ring system could be formed from precursor 3 via a [4 + 2] intramolecular radical cyclization.…”

Me2AlSEt-Promoted Domino Dieckmann Cyclization Enables the Total Synthesis of Polycyclic Polyprenylated Acylphloroglucinols

“…Although the Dieckmann reaction is well established and has been widely used for preparing 1,3dicarbonyl compounds, we are not aware of examples of its use in cascades to construct complex molecules. Evaluation of the commonly used basic conditions, such as those involving t-BuOK, NaH, and LiHMDS, 14 at room temperature gave no reactions (see the Supporting Information for details). However, under heating, the reaction with LiHMDS generated two products, 16 and 17 (3:1), which featured a rare 8membered ring structure (entries 1−3).…”