01773nas a2200217   4500008004100000022001400041245014900055210006900204260000800273300001400281490000700295520096500302100002701267700002501294700001901319700002701338700002101365700002201386700002101408856012601429       2018                        eng d  a1477-052000aTotal synthesis of the potent anti-inflammatory natural product solomonamide A along with structural revision and biological activity evaluation0 aTotal synthesis of the potent antiinflammatory natural product s  cDEC  a9138-91420 v163 aHerein, we report the total synthesis of solomonamide A along with its structural revision for the first time. The natural product possesses very potent anti-inflammatory activity, and it contains a macrocyclic peptide having four consecutive stereocenters on an unnatural amino acid component. The key features in the present synthesis include the application of an Evans aldol reaction, ligand-free Heck macrocyclization and chemoselective oxidations. The challenging task of fixing the stereochemistry of OH at the C5-position was accomplished with the help of DFT calculations, applying a quantum-mechanical (QM)/NMR combined approach. Biological evaluation in a mouse paw edema model revealed that a low dose (0.3 mg kg(-1)) of the synthesized solomonamide A showed 74% reduction at 6 h, which was comparable to a high dose (10 mg kg(-1)) standard drug dexamethasone effect (75% at 6 h). Thus, we further confirmed the revised structure of solomonamide A.1 aJachak, Gorakhnath, R.1 aAthawale, Paresh, R.1 aAgarwal, Heena1 aBarthwal, Manoj, Kumar1 aLauro, Gianluigi1 aBifulco, Giuseppe1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/total-synthesis-potent-anti-inflammatory-natural-product-solomonamide-along-structural