Structurally Modified Cyclopenta[ b]benzofuran Analogues Isolated from Aglaia perviridis

Abstract

Four new cyclopenta[b]benzofuran derivatives based on an unprecedented carbon skeleton (1-4), with a dihydrofuran ring fused to dioxanyl and aryl rings, along with a new structural analogue (5) of 5‴-episilvestrol (episilvestrol, 7), were isolated from an aqueous extract of a large-scale re-collection of the roots of Aglaia perviridis collected in Vietnam. Compound 5 demonstrated mutarotation in solution due to the presence of a hydroxy group at C-2‴, leading to the isolation of a racemic mixture, despite being purified on a chiral-phase HPLC column. Silvestrol (6) and episilvestrol (7) were isolated from the most potently cytotoxic chloroform subfraction of the roots. All new structures were elucidated using 1D and 2D NMR, HRESIMS, IR, UV, and ECD spectroscopic data. Of the five newly isolated compounds, only compound 5 exhibited cytotoxic activity against a human colon cancer (HT-29) and human prostate cancer cell line (PC-3), with IC₅₀ values of 2.3 μM in both cases. The isolated compounds (1-5) double the number of dioxanyl ring-containing rocaglate analogues reported to date from Aglaia species and present additional information on the structural requirements for cancer cell line cytotoxicity within this compound class.

Figure 1.

Structures of compounds 1–7 from Aglaia perviridis

Figure 2.

Select (A) HMBC and (B) NOESY correlations of 1

Figure 3.

Overlay of the experimental spectrum of compound 1 (black line) with the (A) calculated spectra of the (1‴S, 2‴R, 5‴R) (blue) and (1‴R, 2‴S, 5‴S) (red) diastereomers, TD-DFT calculated at the wB97XD/Def2TZVP level. (B) TD-DFT calculated ECD spectra; functional sets are noted in the legend and all calculations were ran with the Def2TZVP basis set

Figure 4.

Selected COSY and HMBC correlations of 5

Figure 5.

Comparison of the ECD spectra of compound 5 and silvestrol (6)