Hybeanones A and B, Two Highly Modified Polycyclic Polyprenylated Acylphloroglucinols from Hypericum beanii

Abstract

Hybeanones A and B (1 and 2), two highly oxygenated and rearranged polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from the aerial parts of Hypericum beanii. Their structures comprising absolute configurations were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Compounds 1 and 2 are defined by a newly assembled cyclopentanone unit fused to a tricyclic γ-lactone unit via a ketone carbonyl. The breakage of C-1/C-2 linkage via retro-Claisen reaction, attack from C-1 to C-19, and Baeyer-Villiger oxidation at C-1/C-23 bond were presumed to be the key steps in the assembly of 1 and 2. The isolates 1 and 2 showed potential acetylcholinesterase (AchE) inhibitory activities, with IC50 values of 21.34 ± 1.48 and 18.79 ± 2.36 µmol/L, respectively.

Intramolecular Tricarbonyl‐Ene Reactions and α‐Hydroxy‐β‐Diketone Rearrangements Inspired by the Biosynthesis of Polycyclic Polyprenylated Acylphloroglucinols

“…Although the biyoulactones were recognized as rearranged PPAPs on their isolation, we suggest a revised biosynthetic pathway that closely mirrors the origin of the hyperireflexolides. The distinctive tricyclic γ-lactone ring system of the biyoulactones is shared by the biosynthetically related hybeanones A and B (7 and 8), isolated from Hypericum beanii, [6] and also hypermonones A, B, C and D (9, 10, 11 and 12) which were found in Hypericum monogynum. [7] Herein, we propose that the hyperireflexolide, biyoulactone, hybeanone and hypermonone polycyclic ring systems are all constructed in nature via sequences of intramolecular carbonyl-ene reactions and α-hydroxy-β-diketone rearrangements.…”

“…Although the biyoulactones were recognized as rearranged PPAPs on their isolation, we suggest a revised biosynthetic pathway that closely mirrors the origin of the hyperireflexolides. The distinctive tricyclic γ‐lactone ring system of the biyoulactones is shared by the biosynthetically related hybeanones A and B ( 7 and 8 ), isolated from Hypericum beanii , [6] and also hypermonones A, B, C and D ( 9 , 10 , 11 and 12 ) which were found in Hypericum monogynum [7] …”

Hyperispirones A and B, spiro-bridged polycyclic polyprenylated acylphloroglucinols with anti-angiogenesis activity from Hypericum beanii

“…Over the past few years, our research group has carried out systematic investigations on PPAPs from Hypericum spp., leading to the discovery of a series of complex PPAPs with promising bioactivities. [16][17][18][19][20][21][22] As a result of our continuing project, two unprecedented PPAPs that simultaneously harbor spiro, bridged, and fused ring systems, namely, hyperispirones A (1) and B (2), were isolated from the aerial parts of H. beanii. Structurally, hyperispirone A (1) possesses a caged heptacyclo [18.3.1.0 1,20 .0 2,17 .0 3,15 .0 6,15 .0 8,13 ]tetracosane ring system composed of a dual-bridged spiro core (rings C-F) fused with a tetrahydronaphthalene (rings A and B) and a cyclopentane (ring G), which to the best of our knowledge is the first PPAP possessing a hepta-carbocyclic skeleton, whereas hyperispirone B (2) features an unparalleled 8-oxa-tetracyclo[7.4.2.0 1,9 ,0 3,7 ]cetane ring system.…”

Bioinspired Total Synthesis of Hyperireflexolides A and B

“…Conversely, treatment of 10 with KOt-Bu at low temperature triggered an exocyclic αhydroxy-β-diketone rearrangement to give diastereomeric ester products 22 and 23 (Scheme 4), which share a similar cyclopentanone scaffold to another highly rearranged PPAP natural product, hybeanone B (24). 26 Based on our biosynthetic hypothesis for the hyperireflexolides and the isolation of both 24 and the closely related hypermonone B (25) from Hypericum plants, 27 it is plausible that 22 and 23 are "undiscovered natural products", and we hope our synthesis will aid their future discovery. 28 In summary, we have achieved two total syntheses of hyperireflexolides A and B.…”