Protection of salvinorin B as standard alkoxyalkyl ethers yielded highly potent kappa opioid receptor agonists. Ethoxymethyl ether 6 is among the most potent and selective kappa agonists reported to date. Fluoroethoxymethyl ether 11 is the first potent, selective fluorinated kappa ligand, with potential use in MRI and PET studies. Further enlargement of the alkoxy group, alkylation of the acetal carbon, or heteroatom substitution all reduced activity. These protecting groups may prove useful in related work not only by enabling the use of harsher synthetic conditions, but potentially by optimizing the potency of the products.