Isolation, Chemical Synthesis and Interconversion of Fusaric Acid Derivatives.

¹ Vanisa Petriti, ² Shugeng Cao, ¹ Yousong Ding, ¹ Guangrong Zheng.

1. Department of Medicinal Chemistry, University of Florida, 1345 Center Dr. Gainesville, FL 326108
2. The Daniel K. Inouye College of Pharmacy, University of Hawaii, 200 W. Kāwili St., Hilo, Hawaiʻi 96720-4091

Fusaric acid and its derivatives are mycotoxins produced by some Fusarium sp. These fungal natural products can lead to contamination of maize and other agricultural foods.  Additionally, some analogs have shown antibiotic, anti-hypertensive and anti-cancer activity. Biosynthetic studies of these compounds can support the development of viable strategies to access these compounds and their analogs.  Recently, two new dimeric analogs were isolated from a marine Fusarium sp. (FM701). Based on their structures, we propose that these compounds can be synthesized through the coupling of fusaric acid and 9-hydroxyfusaric or fusaric acid and 9, 10-dehydrofusaric acid. In this study, we developed concise chemical synthetic routes towards two monomeric derivatives of fusaric acid which were isolated in minute amounts from the culture of FM701. The synthesis of 9-hydroxyfusaric acid and 9, 10-dehydrofusaric acid was achieved in three and five steps from fusaric acid, respectively. Key steps included Sonogashira coupling, Des-Martin oxidation and Julia olefination. We further performed feeding experiments with synthetic analogs to characterize the biosynthesis of two dimeric compounds.  Our preliminary results demonstrated that fusaric Acid, 9-hydroxyfusaric and 9, 10-dehydrofusaric are the precursors of the two new dimeric analogs. Our findings not only shed light on the biosynthetic pathways of these novel dimeric compounds but also open avenues for the potential utilization of these derivatives in various applications.

Preferred presentation day: May 31st (Friday).