Totalsynthesis of Aigialospirol and 7´,8´-Dihydroaigialospirol

• Applicant: Dr. Sarah Wagner
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2012 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 229269156

Marine microorganisms such as bacteria, fungi and microalgae are rich sources of potent bioactive compounds providing structurally interesting compounds for drug discovery programs. Hypothemycin, a 14-membered resorcylic acid lactone (RAL), was first isolated from the fungal strain of hypomyces trichlothecoides in 1980 and was subsequently identified as a moderate protein kinase inhibitor. More recently, Isaka reported the isolation of hypothemycin along with two unique spiroacetals aigialospirol and 7',8' dihydroaigialospirol from the mangrove fungus Aigialus parvus BCC 5311. At present, useful biological activities of both spiroacetals remain unknown. Nonetheless these molecules are interesting structures for the development of bioactive compounds, with special interest in their spiroacetal subunit, which is present in many antibacterial drugs. Biosynthetically, all members of the RAL family of mycotoxins are believed to be derived from the type-I polyketide synthase pathway. Specifically, aigialospirol and 7',8' dihydroaigialospirol were proposed to be synthesized from hypothemycin.The only known total synthesis of aigialospirol was reported by Hsung and coworkers and featured a cyclic ketal-tethered ring-closing metathesis strategy to construct the heterocyclic core. More studies towards the synthesis of aigialospirol or a synthesis of 7',8' dihydroaigialospirol remain unknown until today.Hence, the overall aim of the present research is to synthesize the marine-derived natural products aigialospirol and 7',8'-dihydroaigialospirol in a new total synthesis. Inspired by the biosynthesis of the natural products one key step of the proposed synthesis is a spiroacetalisation as final step. More key steps of the synthesis are a Sonogashira coupling between two building blocks, acetyliden addition and asymmetric Sharpless dihydroxylation of a Z-alkene.

• DFG Programme: Research Fellowships
• International Connection: New Zealand
• Host: Professorin Margaret A. Brimble