Facile Synthesis of Natural Alkoxynaphthalene Analogues from Plant Alkoxybenzenes

Analogues of the bioactive natural alkoxynaphthalene pycnanthulignene D were synthesized by an efficient method. The starting plant allylalkoxybenzenes (<b>1</b>) are easily available from the plant essential oils of sassafras, dill, and parsley. The target 1-arylalkoxynaphthalenes (<b>5</b>) exhibited antiproliferative activity in a phenotypic sea urchin embryo assay

<i>cis</i>-Restricted 3‑Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays

We have synthesized a series of novel <i>cis</i>-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, <b>14a</b>, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds <b>12a</b> and <b>14a</b> displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells