title: Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers.
abstract: 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.
authors.affiliation: Mailman Research Center, McLean Hospital, Belmont, MA 02478, USA. tmunro@mclean.harvard.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Munro
authors.forename: Katharine K
authors.initials: KK
authors.lastname: Duncan
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
authors.forename: Lee-Yuan
authors.initials: LY
authors.lastname: Liu-Chen
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
authors.forename: Cécile
authors.initials: C
authors.lastname: Béguin
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004987:Ethers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008745:Methylation; D015394:Molecular Structure; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000438:Alcohols; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D004987:Ethers; D017473:Receptors, Opioid, kappa; C059688:alkoxyl radical; C508456:salvinorin B