Total synthesis of the potent anti-inflammatory natural product solomonamide A along with structural revision and biological activity evaluation

Abstract

Herein, we report the total synthesis of solomonamide A along with its structural revision for the first time.

Exploring the Antiangiogenic Potential of Solomonamide A Bioactive Precursors: In Vitro and In Vivo Evidences of the Inhibitory Activity of Solo F-OH During Angiogenesis

“…In the last years, different studies toward the synthesis of solomonamides have been reported, mainly by Reddy et al [15,17,37,38,39,40,41]. In fact, very recently, the total syntheses of solomonamides A and B have been reported [13], which led to their stereochemical revision with respect to that initially proposed, and confirmed the anti-inflammatory activities reported for the natural products.…”

“…Such is the case of the potent anti-inflammatory octacyclopeptides perthamides [8,9] and swinholides, with antifungal effect [10] and antiproliferative activity against a number of tumor cells by the disruption of actin cytoskeleton [11]. Together with them, solomonamide A ( 1 ) and B ( 2 ) are two bioactive compounds that have been recently isolated from T. swinhoei and described as exerting a dose-dependent anti-inflammatory activity in vivo [12,13].…”

“…Indeed, the particular geographical niche of T. Swinhoei , which was collected at the Solomon Islands, South Pacific, worsens this limitation. In order to easily obtain solomonamides, different strategies were developed to chemically synthesize them, and very recently, the total syntheses of solomonamides A and B was reported by Reddy et al [13]. Previously, in an effort to reach the complete synthesis of the solomonamides, a new synthetic strategy directed toward these natural products was designed by our group [17].…”

Recent Achievements in Total Synthesis for Integral Structural Revisions of Marine Natural Products

“…Iriomoteolide-2a Incorrect stereochemistry [30,31 ] Incorrect stereochemistry [26] Anabaenopeptin Incorrect stereochemistry [30,31 ] Incorrect stereochemistry [27] Anabaenopeptin Incorrect constitution [34] Xanthone Chemical derivatization…”

Access to a Stereoisomer Library of Solomonamide Macrocycles

“…Here we are reporting syntheses of all possible stereoisomers of solomonamide B macrocycles particularly around AHMOA fragment keeping the alanine stereocenter fixed. Among these, two macrocycles with 2 S , 3 R , 4 R and 2 S , 3 S , 4 S stereochemistry were previously synthesized in our lab during the stereochemical revision of natural products . Synthesis of the remaining six possible stereoisomers is a challenging task and involves remodelling of the synthetic pathways.…”