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-structural02381nas a2200241   4500008004100000022001400041245014100055210006900196260000900265300001600274490000700290520150900297100002701806700001801833700001801851700002501869700002101894700002801915700001901943700002701962700002101989856012902010       2023                        eng d  a0022-326300aComprehensive study on solomonamides: total synthesis, stereochemical revision, and SAR studies toward identification of simplified lead0 aComprehensive study on solomonamides total synthesis stereochemi  cDEC   a17088-171330 v883 a<p>
	Solomonamides, a pair of macrocyclic peptide natural products originating from marine sources, have garnered significant attention within the synthetic community owing to their marked anti-inflammatory efficacy and intricate molecular architectures. In this paper, we present a very detailed investigation into solomonamides, including the challenges associated with the total synthesis, the evolution of our synthetic strategies, structural reassignment, synthesis of all possible stereoisomeric macrocycles, biological assessment, structure-activity relationship (SAR) studies, etc. Within the ambit of this total synthesis, diverse strategies for macrocyclization were rigorously explored, encompassing the Friedel-Crafts acylation, cyclization involving the aniline NH2 moiety, macrolactamization utilizing Gly-NH2, and Heck macrocyclization methodologies. In addition, an array of intriguing chemical transformations were devised, including but not limited to photo-Fries rearrangement, Wacker oxidation, ligand-free Heck macrocyclization, oxidative cleavage of indole, synthesis of contiguous stereocenters via substrate/reagent-controlled protocols, and simultaneous making and breaking of olefinic moieties. The findings of this investigation revealed a structurally simplified lead compound. Remarkably, the lead compound, while possessing structural simplification in comparison to the intricate solomonamide counterparts, demonstrates equipotent in vivo anti-inflammatory efficacy.</p>
1 aJachak, Gorakhnath, R.1 aKashinath, K.1 aVasudevan, N.1 aAthawale, Paresh, R.1 aChoudhury, Rahul1 aDange, Santoshkumar, S.1 aAgarwal, Heena1 aBarthwal, Manoj, Kumar1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/comprehensive-study-solomonamides-total-synthesis-stereochemical-revision-and-sar-studies