First Total Synthesis of Hunanamycin A

Abstract

The first total synthesis of hunanamycin A, an antibiotic natural product with a pyrido[1,2,3-de]quinoxaline-2,3-dione core from a marine-derived Bacillus hunanensis, is disclosed. The present effort provides access to sufficient amounts of scarce hunanamycin A for further biological evaluation and confirmation of the assigned absolute configuration. In addition, four new analogues of the natural product are reported.

Marine natural products

“…185 Hunanamycin A was subsequently synthesised via a simple and scaleable method from 6,7-dimethyl-1,4-dihydroquinoxaline-2,3-dione. 186 189 were obtained when the putative precursors sodium 3,4dihydroxybenzoic acid or shikimic acid were fed to the fungus, reinforcing the proposed shikimate-isoprenoid hybrid biosynthetic pathway. All the metabolites except bicycloalternarenes E 182 and F 183 were weak to moderate inhibitors of NF-kB in RAW264.7 cells.…”

“…185 Hunanamycin A was subsequently synthesised via a simple and scaleable method from 6,7-dimethyl-1,4-dihydroquinoxaline-2,3-dione. 186 An indole alkaloid 161 was obtained from Pantoea agglomerans (mangrove Ceriops tagal, Zhanjiang, Guangdong, China) along with two phenylethylamine derivatives, 3-(p-hydroxy)benzoyl indole 187 and 1,2-di(1H-indol-3-yl)ethane, 188 both known synthetic compounds but now isolated for the rst time as MNPs. 189 Streptomyces sp.…”

Synthesis and Pesticidal Activities of New Quinoxalines

“…New pesticide discovery can be from natural products. Benzopyrazine (quinoxaline) is a fused N-heterocycle found in many natural compounds (Figure ), such as the cyclic peptide triostin A, izumiphenazines A–C, hunanamycin A, , and vitamin B2. , Quinomycins are a type of cyclic oligopeptide antibiotic containing the quinoxaline group in the macrocycles. Izumiphenazines A-C with the quinoxaline group were isolated from Streptomyces species.…”

Route to Benzimidazol-2-ones via Decarbonylative Ring Contraction of Quinoxalinediones: Application to the Synthesis of Flibanserin, A Drug for Treating Hypoactive Sexual Desire Disorder in Women and Marine Natural Product Hunanamycin Analogue

“…As a direct application and to demonstrate the usefulness of the method developed, we decided to perform late-stage transformation on hunanamycin A 34 , an antibiotic natural product derived from marine source, which contains a quinoxaline-2,3-dione core. 12 Hunanamycin showed potent antibiotic activity against Salmonella enterica which causes food poisoning. 13 Pleasingly, the reaction went smoothly to furnish benzimidazol-2-one 35 , a new analogue of hunanamycin A in one step.…”