Synthetic analogues of the antibiotic pestalone

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.…”

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

“…[3] Wegen ihres markanten biologischen Potenzials, der begrenzten Verfügbarkeit aus natürlichen Quellen und ihrer komplexen Struktur [4] sind Pestalon (1) und die Pestalachloride interessante Zielmoleküle für die chemische Synthese. 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.…”

Direct approaches toward natural product synthesis

“…Upon extensively searching the literature, we found that there were no examples of RCM where all positions ortho to the vinyl groups were substituted. 26,27 To test our hypothesis, we decided to synthesize 15 ( Figure 2). …”

“…Prenylation of the iodo compound 32, however, was not straight forward. Although the allylation of 32 under the Stille coupling conditions went smoothly (Scheme 18), the coupling with prenyltributylstannane 25,26 (37) was far more challenging (Table 1). Table 1 We tried a variety of different conditions by modifying the catalyst from palladium …”