A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of β-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated β-anhydroicaritine derivatives were synthesised using this methodology. These newly synthesised derivatives, especially the compounds 5b, 5c and 5j, significantly suppressed cell proliferation when tested against cancer cell lines in vitro. Compound 5j (R = Bn) exhibited a competitive inhibition against MCF7 in vivo compared to tamoxifen.
Keywords: alkylation; anticancer; selectivity; β-anhydroicaritine.