The combretastatins are diaryl stilbenoid natural products isolated from the bark of the South African willow tree Combretum caffrum. CA-4 is a potent anticancer agent, which inhibits cancer cell proliferation and microtubule polymerisation by binding at the colchicine-binding site of tubulin. Only the cis configuration of CA-4 possesses anticancer bioactivity. It readily isomerizes in vivo during metabolism and upon storage into the more thermodynamically stable but significantly less active trans isomer. Our group has reported extensive series of antiproliferative, tubulin-binding β-lactam compounds – the ‘Combretazets’ – over the last decade with aim of overcoming this undesirable in vivo conversion to the inactive trans form. Substituting the ethylene bridge with a 1,4-diaryl-2-azetidinone ring (01) allows similar structural arrangement between CA-4 ’s two aromatic rings and overcomes cis/trans isomerization. The racemic azetidinone 01 has an IC₅₀ value of 4 nM in MCF-7 cells. It is essential to distinguish the eutomer from the distomers. Here, we describe the synthesis, resolution, and biochemical activity of the enantiomers of 01.