The marine sponge derived β2-adrenoceptor agonist S1319 has been synthesized following a six-step linear sequence. Central to the approach employed is the formation of a 7-lithiated- 2, 4-dialkoxybenzothiazole intermediate obtained via a directed-lithiation/benzyne-mediated cyclization reaction. The incorporation of a tert-butyl ether residue into the cyclization precursor for the pivotal ring-closing step has been shown to significantly increase the ...