Standard protecting groups create potent and selective κ opioids: Salvinorin B alkoxymethyl ethers

Protection of salvinorin B as standard alkoxyalkyl ethers yielded highly potent κ opioid receptor agonists. Ethoxymethyl ether 6 is among the most potent and selective κ agonists reported to date. Fluoroethoxymethyl ether 11 is the first potent, selective fluorinated κ 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.

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