The Biomimetic Total Syntheses of the Antiplasmodial Tomentosones A and B

Abstract

The first biomimetic total syntheses of natural phloroglucinols tomentosones A and B and their analogues have been accomplished. The synthetic strategy primarily referred to the potential biosynthetic precursors and their possible sequence of segments assembly by chemological evolution of the structural entities and enabled rapid access of the titled compounds in a practical fashion.

Recent advances in the synthesis of natural products containing the phloroglucinol motif

“…As described previously in the syntheses of rhodomyrtosones A and G (Scheme 16) by Liu, Tan and Hu, 73 further reactions to convert rhodomyrtosone A ( 92 ) to tomentosones A ( 99 , Scheme 18) and B ( 100 ) failed to proceed, suggesting an alternative biosynthetic mechanism which might involve rhodomyrtone ( 98 ) as the biosynthetic intermediate. Tomentosones A ( 99 ) and B ( 100 ), isolated from Rhodomyrtus tomentosa , are phloroglucinol compounds with a complex trimeric-bisfurane–pyrane skeleton.…”

“…66 The Friedel-Cras reaction of 78 with isovaleraldehyde (79) was followed by concomitant heterodimerization of resulting In a related work, Liu, Tan and Hu proposed two possible biosynthetic mechanisms toward trimeric phloroglucinols, one of which involved rhodomyrtosone A (92) as the key intermediate. 73 In view of the biosynthesis, the team modied Porco's work by switching acetic acid to pyridinium p-toluenesulfonate (PPTS) in reuxing toluene to give a mixture of rhodomyrtosones A (92) and G (93) in 2 : 1 ratio via the same process (Scheme 16). 73 The success in the synthesis of rhodomyrtosones prompted Liu, Tan and Hu to construct its structurally-related compound watsonianone B (95, Scheme 17), 74 an antiplasmodial compound from Corymbia watsoniana.…”

“…73 In view of the biosynthesis, the team modied Porco's work by switching acetic acid to pyridinium p-toluenesulfonate (PPTS) in reuxing toluene to give a mixture of rhodomyrtosones A (92) and G (93) in 2 : 1 ratio via the same process (Scheme 16). 73 The success in the synthesis of rhodomyrtosones prompted Liu, Tan and Hu to construct its structurally-related compound watsonianone B (95, Scheme 17), 74 an antiplasmodial compound from Corymbia watsoniana. 75 By adding endoperoxide 91 to 94 in acetic acid, watsonianone B (95) was obtained in 27% yield.…”

“…In a related work, Liu, Tan and Hu proposed two possible biosynthetic mechanisms toward trimeric phloroglucinols, one of which involved rhodomyrtosone A ( 92 ) as the key intermediate. 73 In view of the biosynthesis, the team modified Porco's work by switching acetic acid to pyridinium p -toluenesulfonate (PPTS) in refluxing toluene to give a mixture of rhodomyrtosones A ( 92 ) and G ( 93 ) in 2 : 1 ratio via the same process (Scheme 16). 73…”

“…73 In view of the biosynthesis, the team modified Porco's work by switching acetic acid to pyridinium p -toluenesulfonate (PPTS) in refluxing toluene to give a mixture of rhodomyrtosones A ( 92 ) and G ( 93 ) in 2 : 1 ratio via the same process (Scheme 16). 73…”