First reported in 2001, the irciniasulfonic acids, 1a-c & 2, were isolated from the Japanese marine sponge Ircina sp. and have been reported as potential multidrug resistance (MDR) modulators, reversing MDR at 33 mg/mL against P-gp overexpressing MDR tumor cells (KB/VJ300) in the presence of 10 ng/mL of vincristine.  We herein disclose the first total synthesis of the irciniasulfonic acids via a convergent and flexible approach, that allows for the synthesis of both enantiomers of the natural product and for the incorporation of a range of side chains, enabling optimisation of biological activity.