Hopeanol: A Potent Cytotoxin with A Novel Skeleton from Hopea exalata

Abstract

Hopeanol, a rearranged resveratrol dimer ester with an unprecedent carbon skeleton, was isolated from the bark ofHopea exalata. Its structure was determined by comprehensive spectroscopic analysis. Hopeanol exhibited potent cytotoxicity against six human cancer cell lines with its IC50 = 0.52–19.36 μM. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Hopeahainol A: An Acetylcholinesterase Inhibitor from Hopea hainanensis

“…Hopeahainol B (3), a red amorphous powder, had a molecular formula of C 29 H 18 [4] ] that was confirmed by the [M+H] + ion peak at m/z 499.1033 in its HRE-SIMS analysis (calcd for C 29 H 19 O 9 , 499.1029). Its 1 H and 13 C NMR spectra (Table 2) were well comparable to those of 1 except for that the methoxyl ester signals (d H 3.52, d C 51.8), which was not observed for 4.…”

Total Synthesis of Hopeahainol A and Hopeanol

“…Indeed, exposure of d-lactone 10 to KOtBu in THF at 0! 25 8C led, upon quenching with aqueous NH 4 Cl solution, to olefinic g-lactone 12, which was obtained through anion formation, b-elimination, and ring closure, as a single isomer (76 % yield; Scheme 3). The remaining phenolic group was then protected as an acetate (13, Ac 2 O, DMAP, quantitative yield), and the resulting olefinic product was subjected to epoxidation with mCPBA to afford epoxide 3 as a mixture of diastereoisomers (ca.…”

“…[1] Resveratrol and its oligomeric descendents are particularly interesting owing to their unique structures and important physiological properties as evidenced by the recent surge of research on their chemistry and biology. [2] Hopeahainol A [3] (1, Scheme 1) and hopeanol [3,4] (2, Scheme 1) are two recently disclosed molecules, each thought to be biosynthetically derived from two molecules of resveratrol. Although closely related in structure and biosynthetic origin, their promising biological properties are diverse.…”

“…Originally isolated from Hopea exalata [4] and subsequently from Hopea hainanensis, [3] hopeanol (2) is a cytotoxic agent which is active against a variety of tumor cells, including KB cells (IC 50 = 0.52 mm). Hopeahainol A (1), on the other hand, was isolated from Hopea hainanensis [3] and exhibited inhibitory activity against acetylcholinesterase (IC 50 = 4.33 mm), an enzyme implicated and exploited for the treatment of Alzheimers disease.…”

“…Synthetic racemic 1 and 2 exhibited identical physical properties ( 1 H and 13 C NMR, and mass spectroscopic data) to those reported in the literature. [3,4] The conversion of 17 into hopeahainol A (1) appears to proceed through a labile intermediate (19: X = OH or Br), [9] which collapses to the desired product when placed on a preparative silica gel plate and allowed to stand for a few hours. It is also interesting to speculate that hopeahainol A (1) is locked in its unique structure by the g-lactone ring which pushes carbons C1b and C7a too far apart for interaction, and that it is its rupture with NaOMe (1!20) that allows the skeletal rearrangement (20!…”