title: Design, synthesis, stereochemistry and antioxidant properties of various 7-alkylated 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones.
abstract: We used the modified Mannich condensation to synthesize three closely-related series of 7-alkylated 3-ABNs 1-5 viz., 7-methylated 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (7-Me ABNs 1-5), 7-ethylated 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (7-Et ABNs 1-5) and 7-tert-pentylated 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones (7-tert-pentyl ABNs 1-5). All compounds yielded good as single isomers by the use of PPA·SiO(2) as a heterogeneous Bronsted acidic catalyst. The 1D, 2D NMR, and single-crystal XRD interpretations unambiguously characterized the stereochemistry of the synthesized compounds. In solution as well as solid-state, all compounds exist in the twin-chair conformation with equatorial orientations of all substitutions, despite their nature and positions. The chemical methods viz., DPPH, reducing power, and phospho-molybdenum methods identified some of the target curcumin analogs as active compounds. Among them, 7-Me ABN 4 (7-methyl-2,4-bis(3-methoxy-4-hydroxyphenyl)-3-azabicyclo[3.3.1]nonan-9)-one exerted the best antioxidant profile that comparable to standard l-ascorbic acid, α-tocopherol and curcumin. Hence, we evaluated further for its intracellular ROS inhibition potency on RAW 264.7 macrophage cells, and found to be effective as well as non-toxic at 100 μM.
authors.affiliation: Department of Biomedicinal Chemistry, Inje University, Gimhae 621-749, Gyeongnam, South Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Park
authors.forename: Jayachandran
authors.initials: J
authors.lastname: Venkatesan
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
authors.forename: Paramasivam
authors.initials: P
authors.lastname: Parthiban
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D053961:Azabicyclo Compounds; D017382:Reactive Oxygen Species