Enantioselective Total Synthesis of Blennolide H and Phomopsis‐H76 A and Determination of Their Structure

Abstract

This work reports on the enantioselective total synthesis of the two dimeric natural chromanone lactones phomopsis-H76 A (5) and blennolide H (6). Both syntheses could be achieved from chromane 11, which was obtained by an enantioselective Wacker-type cyclization with >99 % ee. The dimerization of the corresponding monomers was performed using a palladium-catalyzed Suzuki reaction. Moreover, within this work it was possible to revise the absolute configuration of phomopsis-H76 A and determine the relative as well as absolute configuration of blennolide H.

Rigid 3D-spiro chromanone as a crux for efficient antimicrobial agents: synthesis, biological and computational evaluation

“…HePG-2 cell line was cultured in RPMI-1640 medium containing 10% fetal bovine serum and 100 units per mL 1% antibiotic penicillin/streptomycin at 37 °C in a 5% carbon dioxide incubator. After seeding HePG-2 cell line in a 96-well plate (density: 1.0 × 10 4 cells per well) at 37 °C FOR 48 h under 5% carbon dioxide, the cells were treated with different concentration of the synthesized compounds 2–21 and followed by an incubation period for 24 h. After that, 20 μL of pre-prepared MTT soln (5 mg mL −1 ) was added onto each well followed by a second incubation for 4 h. In order to dissolve the generated purple formazan, 100 μL DMSO was added to each well. The spectrophotometric absorbance for each well was measured at 570 nm using microplate reader (ELx800, USA).…”

“…The formed precipitate was ltered off and recrystallized from ethanol to yield 3 as pale grey crystals. Yield ( 1 (4). A stirred solution of aniline (2 mmol, 0.18 mL) in HCl [2 N] (3 mL) in an ice-salt bath was diazotized with a cold solution of sodium nitrite (2 eq, 4 mmol, 0.28 g) in a least amount of water.…”

“…Chromone derivatives constitute one of the main families of heterocyclic compounds. 1 Particularly, 4-chromanones have attracted significant attention because of their wide natural occurrence such as sterubin, 2 morellin, 3 and blennolide 4 ( Fig. 1A ).…”

Enantioselective Total Synthesis of Chromanone Lactone Homo‐ and Heterodimers

“…Monomeric chromanone lactones are gonytolide C ( 5 ) and G, the lachnones C–E, paecilin B and the blennolides D ( 6 )–F . Examples for dimeric chromanone lactones are blennolide H ( 7 ) from Alternaria sp., and phomopsis‐H76 A from Phomopsis sp., which have been synthesized this year (2018) for the first time allowing the determination of their relative and absolute configuration . Quite recently the preparation of an additional natural homodimeric chromanone lactone has been described …”

“…[2] Monomeric chromanone lactones are gonytolide C( 5) [7] and G, [8] the lachnones C-E, [9] paecilin B [10] and the blennolides D( 6)-F. [11] Examples for dimeric chromanonel actones are blennolide H ( 7)f rom Alternaria sp., [12] and phomopsis-H76 Af rom Phomopsis sp., [13] which have been synthesized this year (2018) for the first time allowing the determination of their relative and absolutec onfiguration. [14] Quite recently the preparation of an additional natural homodimeric chromanone lactone has been described. [15] On the other hand, the configuration of several otherc ompounds of this type, especially those with ah eterodimeric structure as paecilin A( 8)f rom Paecilomyces sp.…”