The first total synthesis of SB87-Cl and pestalone, novel bioactive benzophenone natural products

Synthesis of benzophenones from geminal biaryl ethenes using m-chloroperbenzoic acid

“…1- 3 In the past few decades, numerous natural products bearing a benzophenone architecture, such as cariphenones A and B, 4 balanol, 5 Clusiaphenone, 6 and pestalone, 7 have been reported. Molecules built on these scaffolds are known to exhibit a wide range of biological and pharmacological activities, acting as antioxidants, 8 analgesics, 9 protein kinase inhibitors, 10 and antiviral agents.…”

Total Synthesis of the Marine Antibiotic Pestalone and its Surprisingly Facile Conversion into Pestalalactone and Pestalachloride A

“…[3] Owing to their obvious biological potential, their limited availability from natural sources, and their challenging chemical structures, [4] pestalone (1) and its congeners are interesting target molecules for chemical synthesis. Our first study in 2003 resulted in the synthesis of deformylpestalone, [5] and little later a total synthesis of 1 (and its demethylated derivative 2) [6] was communicated by Nishiyama et al [7] Remarkably, no further biological studies have been reported since then. We describe herein a highly efficient and practicable synthesis of 1 which makes it possible for the first time to prepare substantial amounts of this natural product for further chemical and biological studies.…”

“…The selective generation of the mono-O-methylated structure was considered to be possible by appropriate protecting-group manipulations. [5,7] To probe the general feasibility of the concept, we first elaborated a synthesis of per-O-methyl-pestalone 12 (Scheme 2). Starting from commercial 5-methylresorcinol (5), we prepared building block 6 through successive halogenation [5] and double O-methylation.…”

Totalsynthese des marinen Antibiotikums Pestalon und seine einfache Umwandlung in Pestalalacton und Pestalachlorid A

“…Unsere erste Studie führte 2003 zur Synthese von Deformylpestalon, [5] und wenig später beschrieben Nishiyama und Mitarbeiter eine Synthese von 1 und dem demethylierten Derivat 2. [6,7] Seitdem wurden allerdings keine neuen biologischen Daten für 1 publiziert.…”

“…Die selektive Erzeugung des mono-O-methylierten Produktes sollte mithilfe geeigneter Schutzgruppen gelingen. [5,7] Zum Nachweis der generellen Realisierbarkeit dieses Konzeptes erarbeiteten wir zunächst eine Synthese des Per-O-methylpestalons (12; Schema 2). Ausgehend von käufli-chem 5-Methylresorcin (5) wurde der Baustein 6 durch sukzessive Halogenierung [5] und doppelte O-Methylierung erhalten.…”