Bis-indole alkaloids from marine sponges are an intriguing class of natural products with a variety of activities. However, only a preliminary biological study of tulongicin A (5), a related previously isolated marine tris-indole alkaloid, has been conducted. In this study, we accomplished the first asymmetric total synthesis of 5 via the construction of an imidazoline-linked bis-indolylmethane skeleton using a Friedel–Crafts-type reaction. Our synthesis enabled a detailed study of the antibacterial profile of 5. Compound 5 displayed bactericidal activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains.
{"title":"Total Synthesis and Antibacterial Activity of Marine Tris-indole Alkaloid Tulongicin A","authors":"Shuji Tsuruda, Takumi Sato, Hiroshi Aoyama, Natchanun Sirimangkalakitti, Shigeru Fujimura, Mitsuhiro Arisawa* and Kenichi Murai*, ","doi":"10.1021/acs.jnatprod.4c00129","DOIUrl":"10.1021/acs.jnatprod.4c00129","url":null,"abstract":"<p >Bis-indole alkaloids from marine sponges are an intriguing class of natural products with a variety of activities. However, only a preliminary biological study of tulongicin A (<b>5</b>), a related previously isolated marine tris-indole alkaloid, has been conducted. In this study, we accomplished the first asymmetric total synthesis of <b>5</b> via the construction of an imidazoline-linked bis-indolylmethane skeleton using a Friedel–Crafts-type reaction. Our synthesis enabled a detailed study of the antibacterial profile of <b>5</b>. Compound <b>5</b> displayed bactericidal activity against <i>Staphylococcus aureus</i>, including methicillin-resistant <i>S. aureus</i> (MRSA) strains.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1021/acs.jnatprod.3c01177
Liangguang Yi, Shen Tan, Lorenzo V. White, Min-Yi Liang* and Martin G. Banwell*,
The title marine natural products have been prepared by total synthesis and in the case of congeners 3, 6, and 7 for the first time. Each of these was obtained by manipulation of readily prepared denigrin B (2). The structure, 3, assigned to denigrin C is shown to be incorrect. Reaction of compound 2 with DDQ has led, in high yield, to the related natural product spirodactylone (16), while treating the corresponding permethyl ether 15 with PIFA/BF3·Et2O provides compound 20, embodying an isomeric framework.
上述海洋天然产物是通过全合成方法制备的,其中同系物 3、6 和 7 是首次制备。每种同系物都是通过操作容易制备的变性变色菊酯 B (2) 而获得的。3 被认为是变性木酚 C 的结构被证明是不正确的。将化合物 2 与 DDQ 反应,可以高产率地得到相关的天然产物螺内酯(16),而将相应的高甲基醚 15 与 PIFA/BF3-Et2O 处理,可以得到化合物 20,其中包含一个异构体框架。
{"title":"Total Syntheses of the Structures Assigned to Denigrins A, B, C, F, and G, 3,4-Diaryl-Pyrrole and -Pyrrolidinone Alkaloids, and the Conversion of Congener B into the Co-metabolite Spirodactylone","authors":"Liangguang Yi, Shen Tan, Lorenzo V. White, Min-Yi Liang* and Martin G. Banwell*, ","doi":"10.1021/acs.jnatprod.3c01177","DOIUrl":"10.1021/acs.jnatprod.3c01177","url":null,"abstract":"<p >The title marine natural products have been prepared by total synthesis and in the case of congeners <b>3</b>, <b>6</b>, and <b>7</b> for the first time. Each of these was obtained by manipulation of readily prepared denigrin B (<b>2</b>). The structure, <b>3</b>, assigned to denigrin C is shown to be incorrect. Reaction of compound <b>2</b> with DDQ has led, in high yield, to the related natural product spirodactylone (<b>16</b>), while treating the corresponding permethyl ether <b>15</b> with PIFA/BF<sub>3</sub>·Et<sub>2</sub>O provides compound <b>20</b>, embodying an isomeric framework.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-15DOI: 10.1021/acs.jnatprod.4c00336
Jianying Han, Paul V. Bernhardt and Robert J. Capon*,
A chemical investigation of Australian soil-derived bacteria Actinomadura sp. S4S-00069B08 yielded eight new benzenoid ansamycins, goondansamycins A–H. Goondansamycins feature rare 1,4-benzoxazin-3-one or o-diamino-p-benzoquinone moieties and can exist as both aglycones or 9-O-α-glycosides of either d-rhodinose or d-amicetose. Structures were solved on the basis of detailed spectroscopy, including X-ray analysis.
通过对澳大利亚土壤源细菌Actinomadura sp. S4S-00069B08进行化学研究,发现了八种新的苯并ansamycins--鹅丹霉素A-H。Goondansamycins 具有罕见的 1,4-苯并恶嗪-3-酮或邻二氨基对苯醌分子,可以以 d-罗丁糖或 d-氨基乙糖的缩醛或 9-O-α-糖苷的形式存在。通过详细的光谱分析,包括 X 射线分析,这些化合物的结构得到了解决。
{"title":"Goondansamycins A–H: Benzenoid Ansamycins from an Australian Volcanic Crater Soil-Derived Actinomadura sp. S4S-00069B08","authors":"Jianying Han, Paul V. Bernhardt and Robert J. Capon*, ","doi":"10.1021/acs.jnatprod.4c00336","DOIUrl":"10.1021/acs.jnatprod.4c00336","url":null,"abstract":"<p >A chemical investigation of Australian soil-derived bacteria <i>Actinomadura</i> sp. S4S-00069B08 yielded eight new benzenoid ansamycins, goondansamycins A–H. Goondansamycins feature rare 1,4-benzoxazin-3-one or <i>o</i>-diamino-<i>p</i>-benzoquinone moieties and can exist as both aglycones or 9-<i>O</i>-α-glycosides of either <span>d</span>-rhodinose or <span>d</span>-amicetose. Structures were solved on the basis of detailed spectroscopy, including X-ray analysis.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-15DOI: 10.1021/acs.jnatprod.4c00168
Negin Khatibi, Yen-Hua Huang, Conan K Wang, Thomas Durek, Edward K Gilding, David J Craik
Cyclotides are cysteine-rich plant-derived peptides composed of 28-37 amino acids with a head-to-tail cyclic backbone and a knotted arrangement of three conserved disulfide bonds. Their beneficial biophysical properties make them promising molecules for pharmaceutical and agricultural applications. The Violaceae plant family is the major cyclotide-producing family, and to date, every examined plant from this family has been found to contain cyclotides. The presence of cyclotides in Viola communis was inferred by mass spectroscopy previously, but their sequences and properties had yet to be explored. In this study, the occurrence of cyclotides in this plant was investigated using proteomics and transcriptomics. Twenty cyclotides were identified at the peptide level, including two new members from the bracelet (Vcom1) and Möbius (Vcom2) subfamilies. Structural analysis of these newly identified peptides demonstrated a similar fold compared with cyclotides from the same respective subfamilies. Biological assays of Vcom1 and Vcom2 revealed them to be cytotoxic to Sf9 insect cell lines, with Vcom1 demonstrating higher potency than Vcom2. The results suggest that they could be further explored as insecticidal agents and confirm earlier general findings that bracelet cyclotides have more potent insecticidal activity than their Möbius relatives. Seven new cyclotide-like sequences were observed in the transcriptome of V. communis, highlighting the Violaceae as a rich source for new cyclotides with potential insecticidal activity. An analysis of sequences flanking the cyclotide domain in the various precursors from V. communis and other Violaceae plants revealed new insights into cyclotide processing and suggested the possibility of two alternative classes of N-terminal processing enzymes for cyclotide biosynthesis.
{"title":"Isolation and Characterization of Insecticidal Cyclotides from <i>Viola communis</i>.","authors":"Negin Khatibi, Yen-Hua Huang, Conan K Wang, Thomas Durek, Edward K Gilding, David J Craik","doi":"10.1021/acs.jnatprod.4c00168","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00168","url":null,"abstract":"<p><p>Cyclotides are cysteine-rich plant-derived peptides composed of 28-37 amino acids with a head-to-tail cyclic backbone and a knotted arrangement of three conserved disulfide bonds. Their beneficial biophysical properties make them promising molecules for pharmaceutical and agricultural applications. The Violaceae plant family is the major cyclotide-producing family, and to date, every examined plant from this family has been found to contain cyclotides. The presence of cyclotides in <i>Viola communis</i> was inferred by mass spectroscopy previously, but their sequences and properties had yet to be explored. In this study, the occurrence of cyclotides in this plant was investigated using proteomics and transcriptomics. Twenty cyclotides were identified at the peptide level, including two new members from the bracelet (Vcom1) and Möbius (Vcom2) subfamilies. Structural analysis of these newly identified peptides demonstrated a similar fold compared with cyclotides from the same respective subfamilies. Biological assays of Vcom1 and Vcom2 revealed them to be cytotoxic to Sf9 insect cell lines, with Vcom1 demonstrating higher potency than Vcom2. The results suggest that they could be further explored as insecticidal agents and confirm earlier general findings that bracelet cyclotides have more potent insecticidal activity than their Möbius relatives. Seven new cyclotide-like sequences were observed in the transcriptome of <i>V. communis</i>, highlighting the Violaceae as a rich source for new cyclotides with potential insecticidal activity. An analysis of sequences flanking the cyclotide domain in the various precursors from <i>V. communis</i> and other Violaceae plants revealed new insights into cyclotide processing and suggested the possibility of two alternative classes of N-terminal processing enzymes for cyclotide biosynthesis.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-13DOI: 10.1021/acs.jnatprod.4c00049
Mohammed M. A. Ahmed, and , Paul D. Boudreau*,
Bacteria have evolved various strategies to combat heavy metal stress, including the secretion of small molecules, known as metallophores. These molecules hold a potential role in the mitigation of toxic metal contamination from the environment (bioremediation). Herein, we employed combined comparative metabolomic and genomic analyses to study the metallophores excreted by Delftia lacustris DSM 21246. LCMS-metabolomic analysis of this bacterium cultured under iron limitation led to a suite of lipophilic metallophores exclusively secreted in response to iron starvation. Additionally, we conducted genome sequencing of the DSM 21246 strain using nanopore sequencing technology and employed antiSMASH to mine the genome, leading to the identification of a biosynthetic gene cluster (BGC) matching the known BGC responsible for delftibactin A production. The isolated suite of amphiphilic metallophores, termed delftibactins C–F (1–4), was characterized using various chromatographic, spectroscopic, and bioinformatic techniques. The planar structure of these compounds was elucidated through 1D and 2D NMR analyses, as well as LCMS/MS-based fragmentation studies. Notably, their structures differed from previously known delftibactins due to the presence of a lipid tail. Marfey’s and bioinformatic analyses were employed to determine the absolute configuration of the peptide scaffold. Delftibactin A, a previously identified metallophore, has exhibited a gold biomineralizing property; compound 1 was tested for and also demonstrated this property.
{"title":"LCMS-Metabolomic Profiling and Genome Mining of Delftia lacustris DSM 21246 Revealed Lipophilic Delftibactin Metallophores","authors":"Mohammed M. A. Ahmed, and , Paul D. Boudreau*, ","doi":"10.1021/acs.jnatprod.4c00049","DOIUrl":"10.1021/acs.jnatprod.4c00049","url":null,"abstract":"<p >Bacteria have evolved various strategies to combat heavy metal stress, including the secretion of small molecules, known as metallophores. These molecules hold a potential role in the mitigation of toxic metal contamination from the environment (bioremediation). Herein, we employed combined comparative metabolomic and genomic analyses to study the metallophores excreted by <i>Delftia lacustris</i> DSM 21246. LCMS-metabolomic analysis of this bacterium cultured under iron limitation led to a suite of lipophilic metallophores exclusively secreted in response to iron starvation. Additionally, we conducted genome sequencing of the DSM 21246 strain using nanopore sequencing technology and employed antiSMASH to mine the genome, leading to the identification of a biosynthetic gene cluster (BGC) matching the known BGC responsible for delftibactin A production. The isolated suite of amphiphilic metallophores, termed delftibactins C–F (<b>1</b>–<b>4</b>), was characterized using various chromatographic, spectroscopic, and bioinformatic techniques. The planar structure of these compounds was elucidated through 1D and 2D NMR analyses, as well as LCMS/MS-based fragmentation studies. Notably, their structures differed from previously known delftibactins due to the presence of a lipid tail. Marfey’s and bioinformatic analyses were employed to determine the absolute configuration of the peptide scaffold. Delftibactin A, a previously identified metallophore, has exhibited a gold biomineralizing property; compound <b>1</b> was tested for and also demonstrated this property.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-10DOI: 10.1021/acs.jnatprod.4c00364
Neng Wang, Lin-Xi Wan, Xiaohuan Li, Jin-Bu Xu* and Feng Gao*,
Bioinspired skeleton transformation of a tricyclic lathyrane-type Euphorbia diterpene was conducted to efficiently construct a tetracyclic tigliane diterpene on a gram scale via a key aldol condensation. The tigliane diterpene was then respectively converted into naturally rare ingenane and rhamnofolane diterpenes through a semipinacol rearrangement and a visible-light-promoted regioselective cyclopropane ring-opening reaction. This work provides a concise strategy for high-efficiency access to diverse polycyclic Euphorbia diterpene skeletons from abundant lathyrane-type natural products and paves the way for biological activity investigation of naturally rare molecules.
{"title":"Rapid Access to Tigliane, Ingenane, and Rhamnofolane Diterpenes from a Lathyrane Precursor via Biomimetic Skeleton Transformation Strategy","authors":"Neng Wang, Lin-Xi Wan, Xiaohuan Li, Jin-Bu Xu* and Feng Gao*, ","doi":"10.1021/acs.jnatprod.4c00364","DOIUrl":"10.1021/acs.jnatprod.4c00364","url":null,"abstract":"<p >Bioinspired skeleton transformation of a tricyclic lathyrane-type <i>Euphorbia</i> diterpene was conducted to efficiently construct a tetracyclic tigliane diterpene on a gram scale via a key aldol condensation. The tigliane diterpene was then respectively converted into naturally rare ingenane and rhamnofolane diterpenes through a semipinacol rearrangement and a visible-light-promoted regioselective cyclopropane ring-opening reaction. This work provides a concise strategy for high-efficiency access to diverse polycyclic <i>Euphorbia</i> diterpene skeletons from abundant lathyrane-type natural products and paves the way for biological activity investigation of naturally rare molecules.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1021/acs.jnatprod.4c00246
Zong-Yi Zhang, Xin-Hua Gao, Yi Huang, Yao-Yue Fan* and Jian-Min Yue*,
Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A–J (1–10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey’s method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1–10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 μM.
{"title":"Drymariamides A–J, Antiadipogenic Cyclopeptides Incorporating Noncanonical Amino Acids from Drymaria cordata","authors":"Zong-Yi Zhang, Xin-Hua Gao, Yi Huang, Yao-Yue Fan* and Jian-Min Yue*, ","doi":"10.1021/acs.jnatprod.4c00246","DOIUrl":"10.1021/acs.jnatprod.4c00246","url":null,"abstract":"<p >Herein, we report an extensive phytochemical study on the whole plant of <i>Drymaria cordata</i>, which led to the isolation of ten new orbitides, named drymariamides A–J (<b>1</b>–<b>10</b>). Compounds <b>2</b>, <b>3</b>, and <b>5</b> incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey’s method, X-ray diffraction, and electronic circular dichroism analysis. Compounds <b>1</b>–<b>10</b> exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound <b>7</b> showed an EC<sub>50</sub> value of 1.17 ± 0.19 μM.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1021/acs.jnatprod.3c01274
Juliana Monat, Lucía González Altieri, Nicolás Enrique, Daniela Sedán, Darío Andrinolo, Verónica Milesi and Pedro Martín*,
Cannabidiol (CBD), one of the main Cannabis sativa bioactive compounds, is utilized in the treatment of major epileptic syndromes. Its efficacy can be attributed to a multimodal mechanism of action that includes, as potential targets, several types of ion channels. In the brain, CBD reduces the firing frequency in rat hippocampal neurons, partly prolonging the duration of action potentials, suggesting a potential blockade of voltage-operated K+ channels. We postulate that this effect might involve the inhibition of the large-conductance voltage- and Ca2+-operated K+ channel (BK channel), which plays a role in the neuronal action potential’s repolarization. Thus, we assessed the impact of CBD on the BK channel activity, heterologously expressed in HEK293 cells. Our findings, using the patch-clamp technique, revealed that CBD inhibits BK channel currents in a concentration-dependent manner with an IC50 of 280 nM. The inhibition is through a direct interaction, reducing both the unitary conductance and voltage-dependent activation of the channel. Additionally, the cannabinoid significantly delays channel activation kinetics, indicating stabilization of the closed state. These effects could explain the changes induced by CBD in action potential shape and duration, and they may contribute to the observed anticonvulsant activity of this cannabinoid.
{"title":"Direct Inhibition of BK Channels by Cannabidiol, One of the Principal Therapeutic Cannabinoids Derived from Cannabis sativa","authors":"Juliana Monat, Lucía González Altieri, Nicolás Enrique, Daniela Sedán, Darío Andrinolo, Verónica Milesi and Pedro Martín*, ","doi":"10.1021/acs.jnatprod.3c01274","DOIUrl":"10.1021/acs.jnatprod.3c01274","url":null,"abstract":"<p >Cannabidiol (CBD), one of the main <i>Cannabis sativa</i> bioactive compounds, is utilized in the treatment of major epileptic syndromes. Its efficacy can be attributed to a multimodal mechanism of action that includes, as potential targets, several types of ion channels. In the brain, CBD reduces the firing frequency in rat hippocampal neurons, partly prolonging the duration of action potentials, suggesting a potential blockade of voltage-operated K<sup>+</sup> channels. We postulate that this effect might involve the inhibition of the large-conductance voltage- and Ca<sup>2+</sup>-operated K<sup>+</sup> channel (BK channel), which plays a role in the neuronal action potential’s repolarization. Thus, we assessed the impact of CBD on the BK channel activity, heterologously expressed in HEK293 cells. Our findings, using the patch-clamp technique, revealed that CBD inhibits BK channel currents in a concentration-dependent manner with an IC<sub>50</sub> of 280 nM. The inhibition is through a direct interaction, reducing both the unitary conductance and voltage-dependent activation of the channel. Additionally, the cannabinoid significantly delays channel activation kinetics, indicating stabilization of the closed state. These effects could explain the changes induced by CBD in action potential shape and duration, and they may contribute to the observed anticonvulsant activity of this cannabinoid.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The first total synthesis of bipenicilisorin (1) isolated from Penicillium chrysogenum SCSIO 41001 via its monomer natural product, penicilisorin (2), was achieved. Penicilisorin was synthesized in four steps from a o-bromobenzaldehyde derivative via the Pd-catalyzed one-pot fluorocarbonylation/lactonization/β-elimination cascade reaction. Iodination of penicilisorin gave 7-iodopenicilisorin which was dimerized by Pd-catalyzed homodimerization to provide (±)-bipenicilisorin. The unknown absolute configuration of naturally occurring (+)-bipenicilisorin was examined by optical resolution of the (±)-synthetic bipenicilisorin and a comparison of experimental and theoretical electronic circular dichroism (ECD) spectra. These results support the absolute configuration of the natural product to be Sa. A cytotoxic activity test of (+)-and (−)-bipenicilisorin using A549 cells revealed that (+)-1 has a lower IC50 value than (−)-1.
{"title":"Total Synthesis of Bipenicilisorin and Assignment of the Absolute Configuration","authors":"Eigo Fukuda, Ibuki Fujiwara, Shoki Maruno, Kaiki Motomura, Seiya Endo, Arihiro Iwasaki, Tatsuya Fukuta, Atsushi Nakayama* and Tetsuro Shinada*, ","doi":"10.1021/acs.jnatprod.4c00114","DOIUrl":"10.1021/acs.jnatprod.4c00114","url":null,"abstract":"<p >The first total synthesis of bipenicilisorin (<b>1</b>) isolated from <i>Penicillium chrysogenum</i> SCSIO 41001 via its monomer natural product, penicilisorin (<b>2</b>), was achieved. Penicilisorin was synthesized in four steps from a <i>o</i>-bromobenzaldehyde derivative via the Pd-catalyzed one-pot fluorocarbonylation/lactonization/β-elimination cascade reaction. Iodination of penicilisorin gave 7-iodopenicilisorin which was dimerized by Pd-catalyzed homodimerization to provide (±)-bipenicilisorin. The unknown absolute configuration of naturally occurring (+)-bipenicilisorin was examined by optical resolution of the (±)-synthetic bipenicilisorin and a comparison of experimental and theoretical electronic circular dichroism (ECD) spectra. These results support the absolute configuration of the natural product to be <i>S</i><sub>a</sub>. A cytotoxic activity test of (+)-and (−)-bipenicilisorin using A549 cells revealed that (+)-<b>1</b> has a lower IC<sub>50</sub> value than (−)-<b>1</b>.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1021/acs.jnatprod.3c01175
Zhen Ying, Xiao-Ming Li, Sui-Qun Yang, Hong-Lei Li, Xin Li, Bin-Gui Wang and Ling-Hong Meng*,
A chemical investigation of a cold-seep-sediment-derived fungus, Pseudallescheria boydii CS-793, resulted in characterization of 10 novel bergamotene-derived sesquiterpenoids, pseuboyenes A–J (1–10). Their structures were elucidated by spectroscopic and X-ray crystallographic analyses as well as using the modified Mosher’s method. Compound 1 represents the first example of a β-bergamotene containing a 6-oxobicyclo[3.2.1]octane nucleus adducted with a methyl lactate unit, while 8–10 involve a skeletal rearrangement from bergamotene. Compounds 2–5 showed significant antifungal activities against Colletotrichum gloeosporioides Penz. and Fusarium oxysporum with MICs ranging from 0.5 to 8 μg/mL. Compound 4 exhibited an in vitro anti-F. proliferatum effect with an EC50 value of 1.0 μg/mL.
{"title":"Antifungal Pseuboyenes A–J, Bergamotene-Derived Sesquiterpenoids from a Cold-Seep-Derived Pseudallescheria boydii","authors":"Zhen Ying, Xiao-Ming Li, Sui-Qun Yang, Hong-Lei Li, Xin Li, Bin-Gui Wang and Ling-Hong Meng*, ","doi":"10.1021/acs.jnatprod.3c01175","DOIUrl":"10.1021/acs.jnatprod.3c01175","url":null,"abstract":"<p >A chemical investigation of a cold-seep-sediment-derived fungus, <i>Pseudallescheria boydii</i> CS-793, resulted in characterization of 10 novel bergamotene-derived sesquiterpenoids, pseuboyenes A–J (<b>1</b>–<b>10</b>). Their structures were elucidated by spectroscopic and X-ray crystallographic analyses as well as using the modified Mosher’s method. Compound <b>1</b> represents the first example of a <i>β</i>-bergamotene containing a 6-oxobicyclo[3.2.1]octane nucleus adducted with a methyl lactate unit, while <b>8</b>–<b>10</b> involve a skeletal rearrangement from bergamotene. Compounds <b>2</b>–<b>5</b> showed significant antifungal activities against <i>Colletotrichum gloeosporioides</i> Penz. and <i>Fusarium oxysporum</i> with MICs ranging from 0.5 to 8 <i>μ</i>g/mL. Compound <b>4</b> exhibited an <i>in vitro</i> anti-<i>F. proliferatum</i> effect with an EC<sub>50</sub> value of 1.0 <i>μ</i>g/mL.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}