Total Synthesis and Cytotoxic Activity of 5′‐Hydroxyzearalenone and 5′β‐Hydroxyzearalenone

Abstract

An efficient and convergent synthesis of 5′‐hydroxyzearalenone and 5′β‐hydroxyzearalenone, 14‐membered β‐resorcylic acid lactone (RAL) natural products, has been achieved in a longest linear sequence of 19 steps, and a total of 29 steps, starting from commercially available 5‐hexen‐1‐ol and methyl 2‐(3,5‐dimethoxyphenyl)acetate. The key features of our synthesis include a Jacobsen hydrolytic kinetic resolution, a Mitsunobu esterification and (an E)‐selective ring‐closing metathesis (RCM). Our synthesis also highlights the utility of the acetal protecting group for the resorcylate moiety, and its compatibility with RCM reactions for the synthesis of 14‐membered RALs. The cytotoxic activity of both synthetic compounds was evaluated against seven human cancer cell lines. 5′‐Hydroxyzearalenone shows more potent cytotoxic activity against most of the cancer cell lines tested than its epimer, 5′β‐hydroxyzearalenone. Both compounds show significant cytotoxic activity against the C33A cervical cancer cell line, with IC50 values of 21.33 ± 6.43 µm and 16.00 ± 12.17 µm, respectively.

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

“…Additionally, the diazocine 4b was converted into the divinyldiazocine 7 . Towards this end, the hydroxy groups were tosylated, followed by elimination with potassium butoxide [35–36].…”

An Improved Synthesis of the Triethylene Glycol-Substituted 4-(N-Methyl-N-Boc-Amino)Styrylpyridine

“…Our initial strategy to prepare 3 from 22 consisted of two reactions, β-elimination and then N -methylation. Generally, β-elimination of the tosyl group was carried out in THF with t -BuOK as the base to prepare Boc-protected vinylaniline ( 2 ). , However, as shown in Scheme , the products were affected by the equivalent of t -BuOK. When 1–4 equiv of t -BuOK was screened, besides target compound 2 , a substituted byproduct dimer ( 2a ) and trimer ( 2b ) were also observed through intermolecular substitution; interestingly, 5 equiv of t -BuOK was required for a complete conversion from 22 to 2 for over 2 h. The optimization process is detailed in Table .…”

Short Total Synthesis of (±)-Gelliusine E and 2,3′-Bis(indolyl)ethylamines via PTSA-Catalyzed Transindolylation

“…The cytotoxic activity of all compounds was evaluated against two human breast carcinoma cell lines (MDA-MB-231 and MCF-7) as well as one monkey kidney noncancerous cell line (Vero) by the MTT assay using the general procedure previously described . Cells were exposed to various concentrations of the tested compounds [0–100 μM; 0.2% (v/v) dimethylsulfoxide (DMSO)] and incubated for 72 h. Doxorubicin (0–1 μM) (MedchemExpress, USA) was used as a positive control.…”