Total synthesis of (3R,16E,20E,23R)-(−)-eushearilide and structural determination of naturally occurring eushearilide

Tonoi, Takayuki; Kawahara, Ryo; Yoshinaga, Yutaka; Inohana, Takehiko; Fujimori, Keiko; Shiina, Isamu

doi:10.1016/j.tetlet.2015.01.181

Cited by 11 publications

(8 citation statements)

References 24 publications

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“…We performed a phylogenetic analysis of their HR-PKS genes and a detailed analysis of each cluster and thus showed an unprecedented family of macrolide biosynthetic gene clusters including a glycosylphosphatidylinositol–ethanolamine phosphate transferase (GPI-EPT) homologue gene (see Figures S1B and S1C in the Supporting Information). According to the function of GPI-EPT in eukaryotes, these clusters may be responsible for the biosynthesis of macrolides bearing phosphoethanolamine or its analogues, such as eushearilide ( Eupenicillium shearii ), as well as JBIR-19 and JBIR-20 ( Metarhizium sp. fE61) (see Figures B and C).…”

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Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues

et al. 2020

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Experimental equipment Analytical TLC were performed on silica gel 60 F254 (Merck) and RP-18 F254 (Merck). Column chromatography was carried out on silica gel 60 (70-230 and 40-50 mesh). The NMR spectra were recorded on a Bruker AVANCE III 500 spectrometer (1 H NMR, 500 MHz; 13 C NMR, 125 MHz) or a JEOL ECA-600 (1 H NMR, 600 MHz; 13 C NMR, 150 MHz). Chemical shifts for 1 H and 13 C NMR are given in parts per million (d) relative to tetramethylsilane (dH 0.00) and residual solvent signals (dC 77.0) for CDCl3, (dH 3.30, dC 49.0) for CD3OD and (dH 7.16, dC 128.4) for C6D6 as internal standards. Mass spectra were measured on Exactive Orbitrap Mass Spectrometer (Thermo Fischer Scientific). IR was measured on a JASCO FVS-6000 spectrometer. UV spectra were recorded on a JASCO-V-730 spectrophotometer. HPLC analysis was performed on a JASCO AS-1555-10 Intelligent Sampler, a JASCO PU-4180 RHPLC Pump, a JASCO MD-4017 Photo Diode Array Detector (JASCO), which equipped with a COSMOSIL Packed Column 5C18-MS-II (φ4.6 mm×150 mm) (Nacalai tesque). Fungal material Aspergillus kawachii IFO 4308 and Colletotrichum incanum MAFF 238704 were obtained from Biological Resource Center, NITE (NBRC) and Ministry of Agriculture, Forestry Fisheries (MAFF) respectively. Each fungus was cultured in a PDB liquid medium for 3 days and the cultured mycelium was ground to a fine powder in liquid N2. To the mycelial powder in 1.5 mL tube, 100 µL TE buffer and lysis solution (SDS 1g, 2.5 mL Tris-HCl buffer (1 M), EDTA•2Na•2H2O 186 mg, NaCl 292 mg, 50 mL mQ) were added, gently inverted and incubated 5 min on ice. After centrifugation at 15,000 rpm, 4ºC, for 20 min, 100 µL of the supernatants were transferred to a new 1.5 mL tube, followed by phenol extraction using Phenol: Chloroform: Isoamyl Alcohol 25:24:1 (pH 5.2, Nacalai tesque) and ethanol precipitation. After centrifugation again, TE buffer were added to the pellet of DNA. The DNA solutions of A. kawachii and C. incanum were used as a template for cloning of akmlA-D and cimlA-D respectively. Heterologous host strains Aspergillus oryzae NSAR1 (niaD − , sC − , DargB, adeA −) S1 was used as the host for fungal expression. Escherichia coli Dh5a (TAKARA) was used for the cloning of akmlA-D and cimlA-D. Culture medium Culture medium for A. kawachii IFO 4308 and C. incanum MAFF 238704 PDB (agar) medium: Potato-Dextrose Broth (DIFCO) 7.2 g (and agarose (Nacalai tesque) 4.5 g) in 300 mL distilled water. CPS medium (0.015% adenine): Czapek-Dox Broth (Difco) 1.05 (2.63) g, peptone* 0.3 (0.75) g, Soluble Starch (Nacalai tesque) 0.6 (1.5) g, Maltose Monohydrate (Nacalai tesque) 0.3 (0.75) g and adenine 9 (22.5) mg in 60 (150) mL distilled water. *peptone: mixture of 0.2 (0.5) g of soy peptone, casein peptone and meat peptone (Nacalai tesque). MYG medium: Bacto Peptone (DIFCO) 0.06 g, Bacto Malt Extract (DIFCO) 1.2 g, D-(+)glucose (Nacalai tesque) in 60 mL distilled water. Culture medium for A. oryzae NSAR1 PDB agar medium (adenine 0.05%, arginine 0.1%): Potato-Dextrose Broth (DIFCO) 7.2 g and agarose (Nacala...

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Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues

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“…Our previous work has concerned the unique structural characteristics and promising structure–activity relationship of eushearilide and the total synthesis of this novel antibiotic. In 2015, the total syntheses of 1 and its diastereomers, (3 R ,16 Z ,20 E ,23 R )- and (3 S ,16 Z ,20 E ,23 R )- 1 , were achieved [6,7]. From the results of detailed NMR analyses of these compounds, it was found that natural eushearilide comprises a (16 E ,20 E ) configuration (as shown in eushearilide ( 2 )) and not a (16 Z ,20 E ) configuration of the nonconjugated diene moiety at the C16 and C20 carbons.…”

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Total Synthesis and Antimicrobial Evaluation of 23-Demethyleushearilide and Extensive Antimicrobial Evaluation of All Synthetic Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide

et al. 2019

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A novel stereoisomer of eushearilide, 23-demethyleushearilide, was synthesized, and the structure–activity relationships of this compound along with known eushearilide stereoisomers were investigated in order to design novel lead compounds for the treatment of fungal infections. It was discovered that all of these congeners, together with the natural product, exhibited a wide range of antimicrobial activity against not only fungi but also against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

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“…On the other hand, the relative and absolute configuration at the C3 and C23 chiral centers of eushearilide was not known before our synthesis. Therefore, we initiated a project aimed at the total synthesis of eushearilide so as to clarify the absolute stereochemistry of the natural product and to promote studies of its structure–activity relationship (SAR). , Thus, we have recently achieved enantioselective total synthesis of (3 S ,16 E ,20 E ,23 S )-(+)- 1 , the naturally occurring eushearilide, as shown in Figure , which is found to exhibit significant antimicrobial activity against a variety of fungi and bacteria …”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we initiated a project aimed at the total synthesis of eushearilide so as to clarify the absolute stereochemistry of the natural product and to promote studies of its structure−activity relationship (SAR). 3,4 Thus, we have recently achieved enantioselective total synthesis of (3S,16E,20E,23S)-(+)-1, the naturally occurring eushearilide, as shown in Figure 1, which is found to exhibit significant antimicrobial activity against a variety of fungi and bacteria. 5 On the basis of this result, we next focused our efforts on the preparation of eushearilide stereoisomers to further explore their biological activities.…”

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Total Synthesis and Antimicrobial Activities of All Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide

et al. 2018

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As promising antifungal agents, the eight stereoisomers of eushearilide, including the natural compound, were synthesized relying on an asymmetric Mukaiyama aldol reaction, Julia-Kocienski olefination, and Shiina macrolactonization. Moreover, their in vitro antimicrobial activities against some fungi and bacteria were evaluated by the disk-diffusion method, which revealed that not only natural eushearilide but also its stereoisomers exhibited significant antimicrobial activity against a variety of fungi and bacteria.

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Total synthesis of (3R,16E,20E,23R)-(−)-eushearilide and structural determination of naturally occurring eushearilide

Cited by 11 publications

References 24 publications

Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues

Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)–Ethanolamine Phosphate Transferase Homologues

Total Synthesis and Antimicrobial Evaluation of 23-Demethyleushearilide and Extensive Antimicrobial Evaluation of All Synthetic Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide

Total Synthesis and Antimicrobial Activities of All Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide

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