title: Synthesis of a tetrasubstituted tetrahydronaphthalene scaffold for α-helix mimicry via a MgBr2-catalyzed Friedel-Crafts epoxide cycloalkylation.
abstract: α-Helices are ubiquitous protein recognition elements that bind diverse biomolecular targets. The synthesis of a small molecule scaffold to present the side chains of an α-helix is described. The 1,3,5,7-tetrasubstituted 1,2,3,4-tetrahydronaphthalene scaffold, providing mimicry of the i, i+3, and i+4 positions of an α-helix, was synthesized using a novel MgBr2-catalyzed Friedel-Crafts epoxide cycloalkylation as the key step. Each position may be differentiated via O-alkylation after scaffold synthesis, generating a diversity-oriented approach to readily synthesize proteomimetics for different targets.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.
authors.forename: Devan
authors.initials: D
authors.lastname: Naduthambi
authors.forename: Santosh
authors.initials: S
authors.lastname: Bhor
authors.forename: Michael B
authors.initials: MB
authors.lastname: Elbaum
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Zondlo
mesh_terms: D000478:Alkylation; D001965:Bromides / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D017616:Magnesium Compounds / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001965:Bromides; D017616:Magnesium Compounds; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; C031721:naphthalene; C586611:magnesium bromide; D008274:Magnesium
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