title: Efficient synthesis of anacardic acid analogues and their antibacterial activities.
abstract: Anacardic acid derivatives exhibit a broad range of biological activities. In this report, an efficient method for the synthesis of anacardic acid derivatives was explored, and a small set of salicylic acid variants synthesised retaining a constant hydrophobic element (a naphthyl tail). The naphthyl side chain was introduced via Wittig reaction and the aldehyde installed using directed ortho-metalation reaction of the substituted o-anisic acids. The failure of ortho-metalation using unprotected carboxylic acid group compelled us to use directed ortho-metalation in which a tertiary amide was used as a strong ortho-directing group. In the initial route, tertiary amide cleavage during final step was challenging, but cleaving the tertiary amide before Wittig reaction was beneficial. The Wittig reaction with protected carboxylic group (methyl ester) resulted in side-products whereas using sodium salt resulted in higher yields. The novel compounds were screened for antibacterial activity and cytotoxicity. Although substitution on the salicylic head group enhanced antibacterial activities they also enhanced cytotoxicity.
authors: Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia.
authors: Sreeman K
authors: SK
authors: Mamidyala
authors: Soumya
authors: S
authors: Ramu
authors: Johnny X
authors: JX
authors: Huang
authors: Avril A B
authors: AA
authors: Robertson
authors: Matthew A
authors: MA
authors: Cooper
mesh_terms: D048729:Anacardic Acids / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D020156:Salicylic Acid / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D048729:Anacardic Acids; D000900:Anti-Bacterial Agents; C088115:anacardic acid; D020156:Salicylic Acid