Total synthesis of the potent anti-inflammatory natural product solomonamide A along with structural revision and biological activity evaluation
| Title | Total synthesis of the potent anti-inflammatory natural product solomonamide A along with structural revision and biological activity evaluation |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Jachak, GR, Athawale, PR, Agarwal, H, Barthwal, MKumar, Lauro, G, Bifulco, G, D. Reddy, S |
| Journal | Organic & Biomolecular Chemistry |
| Volume | 16 |
| Issue | 47 |
| Pagination | 9138-9142 |
| Date Published | DEC |
| Type of Article | Article |
| ISSN | 1477-0520 |
| Abstract | Herein, 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. |
| DOI | 10.1039/c8ob02713g |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 3.423 |
Divison category:
Organic Chemistry
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