Facile synthesis of corticiolic acid-a bioactive pharmacophore from natural sources
Sunil Kumar Deevi1, Bhadra Anilkumar1, Priyanka Gladys Pinto2
1Dhanvanthri Lab, Department of Chemistry, Amrita School of Physical Sciences, Amrita Vishwa Vidyapeetham Coimbatore-641112 Tamil Nadu India n_pandurangan@cb.amrita.edu.
Abstract:
Fungal strains have inspired us to find the untapped sources of secondary metabolites. Corticiolic acid (CA, 2,4-dihydroxy-6-pentadecylbenzoic acid; from fungus, Hapalopilus mutans) is one of the core active scaffolds in natural compounds such as Aquastatin-A, B, & C. CA can also be isolated from the plant Lysimachia japonica. CA is a selective inhibitor of PTB1B, a crucial biomarker for anti-diabetic activity. Herein, we report the total synthesis of corticiolic acid achieved via the 9-BBN-based reductive Suzuki-Miyaura coupling of aryl bromide and pentadecane, a key reaction in this strategy. Further, this approach has been explored for the protection-free synthesis of corticiolic acid. The improved synthesis is short, requires mild reaction conditions, and avoids the use of hydrogenation and pyrophoric reagents. Further, the reaction is scalable and does not require protection-deprotection steps. Preliminary studies on cancer cells indicated that corticiolic acid and cordol significantly inhibited the proliferation of HepG2, N2A, and CaCo-2 cancer cells.
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