Spicarins A–D from acetylated extract of fungus Spicaria elegans KLA03

Abstract

5Spicarins A (1) and B (2), two novel isobenzfuran-aspochalasin heterodimers, and spicarins C (3) and D (4), two isobenzofuran dimers, were isolated from the acetylated products of the marine-derived fungus Spicaria elegans KLA03. The structures of compounds 1-4 were elucidated by spectroscopic and/or Xray diffraction methods. Compounds 3 and 4 inhibited lipopolysaccharide (LPS)-induced nitric oxide production in BV2 microglial cells.

Total Syntheses of Asperchalasines A–E

“…Thei dentity of 36 was verified by comparing its spectroscopic data with those of spicarin B, an artificial natural product reported by Zhu and co-workers. [15] Encouraged by this result, we moved to make asperchalasines B-E (1-4)using the mono-methylated hemiacetal 37 (Schemes S2) as the reaction partner. To our delight, 37 turned out to be as uperior substrate by providing four heterodimers asperchalasines B-E (1-4)( 1:4:2:3 = 10:2:1:1) in an otably improved combined yield (80 %).…”

“…Motivated by such unmet challenges and our continuous interest in the cytochalasans family, [7] we set out to explore the total syntheses of these targets upon their disclosure.H erein, we reported the first and collective total syntheses of asperchalasines A-E as well as related congeners. It was assumed that all of these targets could arise from two common precursors,a spochalasin B ( 14) [3c-e] and epicoccine (15), [4] through either heterodimerization or -trimerization. It was assumed that all of these targets could arise from two common precursors,a spochalasin B ( 14) [3c-e] and epicoccine (15), [4] through either heterodimerization or -trimerization.…”

“…[*] R. Bao, C. Tian Our strategy for the synthesis of asperchalasines was mainly built on their plausible biosynthetic origins ( Figure 2). It was assumed that all of these targets could arise from two common precursors,a spochalasin B ( 14) [3c-e] and epicoccine (15), [4] through either heterodimerization or -trimerization. In af orward sense,e picoccine (15) could undergo oxidation to yield the o-quinone species 16 a and 16 b which may further isomerize to the isobenzofuran 16 c.O nce generated, 16 c could react with aspochalasin B( 14)t hrough an intermolecular Diels-Alder reaction.…”

Construction of a Meroterpenoid‐Like Compounds Library Based on Diversity‐Enhanced Extracts

“…The subsequent isolation of each compound produced from such reactions affords a diverse natural‐product‐like library of new molecular scaffolds. There have also been some reports on similar methods that chemically convert natural extracts . However, we defined diversity‐enhanced extracts as natural extracts formed by multiple diversity‐generating reactions that not only convert functional groups, but also form new carbon–carbon bonds and modify the molecular scaffolds similarly to diversity‐oriented synthesis.…”

“…There have also been some reports on similar methodst hat chemically convert natural extracts. [6][7][8][9][10][11] However, we defined diversity-enhanced extracts as natural extracts formed by multiple diversity-generating reactions that not only convert functional groups, buta lso form new carbon-carbon bonds and modify the moleculars caffolds similarly to diversity-oriented synthesis.…”