Ascospiroketals A and B, Unprecedented Cycloethers from the Marine-Derived Fungus Ascochyta salicorniae

Abstract

Chemical investigation of the marine-derived fungus Ascochyta salicorniae led to the isolation of two novel natural products, ascospiroketals A (1) and B (2). From a biosynthetic standpoint, the compounds possess new ring systems. [structure: see text].

Total Synthesis of Ascospiroketal A Through a AgI‐Promoted Cyclization Cascade

“…Repetition of the final two reactions using the stereochemically unique side chains 19, ent-16, and ent-19 gave the candidate stereostructures 35, 36, and 37, respectively ( Figure 2). The specific rotation for 37 ([a] 20 D =+ 5 (c 0.20 in MeOH)) was also consistent in sign with that reported for the natural product ([a] 20 D + 20 (c 0.45 in MeOH)), [1] confirming the absolute stereochemistry of ascospiroketal A as shown for 37. Notably, only the spectra derived from the C15-(S) diastereomers 34 and 37 contained H14a/H14b resonances characteristic of ascospiroketal A (see truncated spectra, Figure 2).…”

Total Synthesis and Configurational Assignment of Ascospiroketal A

“…As indicated in entries 1a nd 2, several protic acids failed to induce equilibration or led to the formation of furan byproducts (entry 2). Addition of BF 3 ·OEt 2 (entry 3) to am ixture of spiroacetale pimers wase ffective in altering the ratio of these compounds in favor of the desired epimer 47,w hile TMSOTf (entry 4) promoted decomposition and other Lewis acids (e.g.,S c(OTf) 3 ,Y b(OTf) 3 ,I nCl 3 ,T i(OiPr) 4 ) failed to effect anomerization.F ortunately,t reatment of the mixture of spiroacetals with ZnCl 2 (entries 9a nd 10) provided am ixture of spiroacetals favoring 47 in ratios of up to approxi-mately2:1. While this ratio is modest when compared to those reported by Kishi [30] and Dudley [28] for relateds ystems, the equilibration provideda na venuef or the recycling of 46 that would ultimately find use in the total synthesis of ascospiroketal A(vide infra).…”

“…[1,2] In 2007, following asystematic investigationo fc ultivation parameters, Kçnig and co-workers isolated two structurally unprecedented polyketides from A. salicorniae:a scospiroketalsA (1) and B( 2)( Figure1). [3] Extensive analysis of their 1D and 2D NMR spectroscopicd ata revealedt hat 1 and 2 both contain ar are octaketide tricyclicc ore, and the quaternary stereogenic center at C2 was postulated to arise from geminal biomethylation by S-adenosyl methionine (SAM). [4] Biosynthetically, 1 and 2 were proposedt od erive from the direct cyclization of the C2-methylated polyketide 3 via distinct pathways that involve formationof at ricyclict etrahydrofuran 4 or lactone 5.…”

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

“…When the dimethyl adduct 6 was submitted to the same conditions, a new product [39–45] 41 was formed besides the dioxanes 39 and 40 (Scheme 7). Its structure was unambiguously established as the spirocyclic dimer 41 by single-crystal X-ray diffraction analysis.…”