Two concise routes for the first total synthesis of Sparstolonin B (SsnB) have been described. The synthesis of SsnB could be accomplished in 5 and 6 steps with 40% and 38% overall yield, respectively. The rhodium-catalysed oxidative coupling of benzoic acid with internal alkyne was used in both strategies to construct the core structure of SsnB.Sparstolonin B (SsnB) is the rst novel bioactive natural small molecule, isolated from a Chinese herb, Sparganium stoloniferum, by Liang and coworkers, which selectively blocks toll-like receptors 2 (TLR2) and TLR4 mediated inammatory signalling by inhibiting the recruitment of MyD88 to the Toll/Il-1 receptor homologue domains of TLR2 and TLR4.