Catalysis-Enabled Access to Cryptic Geldanamycin Oxides

2020 ◽  
Author(s):  
Margaret J. Hilton ◽  
Christopher Brackett ◽  
Brandon Q. Mercado ◽  
Brian S. J. Blagg ◽  
Scott Miller
Keyword(s):  
Natural Product ◽  
Reaction Pathway ◽  
Outer Sphere ◽  
Oxidation Reactions ◽  
Biological Assays ◽  
Peptide Catalysts ◽  
Isolation And Characterization ◽  
Site Selective ◽  
New Compounds ◽  
Stereoselective Oxidation

Catalytic, selective modifications of natural products can be a fertile platform for unveiling not only new natural product analogs with altered biological activity, but also for revealing new reactivity and selectivity hierarchies for embedded functional groups in complex environments. Motivated by these intersecting aims, we report site and stereoselective oxidation reactions of geldanamycin facilitated by aspartyl-peptide catalysts. Through the isolation and characterization of four new geldanamycin oxides, we discovered a synergistic effect between lead peptide-based catalysts and geldanamycin, resulting in an unexpected reaction pathway. Curiously, it seems unlikely that our discoveries would not have been possible absent the outer sphere interactions intrinsic to both the catalyst and the natural product. The result is a set of new “meta” catalytic reactions that deliver both unknown and previously incompletely characterized geldanamycin analogs. Enabled by the catalytic, site-selective epoxidation of geldanamycin, biological assays were carried out to document the bioactivities of the new compounds.<div><br></div>

scholarly journals Catalysis-Enabled Access to Cryptic Geldanamycin Oxides

2020 ◽  
Author(s):  
Margaret J. Hilton ◽  
Christopher Brackett ◽  
Brandon Q. Mercado ◽  
Brian S. J. Blagg ◽  
Scott Miller
Keyword(s):  
Natural Product ◽  
Reaction Pathway ◽  
Outer Sphere ◽  
Oxidation Reactions ◽  
Biological Assays ◽  
Peptide Catalysts ◽  
Isolation And Characterization ◽  
Site Selective ◽  
New Compounds ◽  
Stereoselective Oxidation

Catalytic, selective modifications of natural products can be a fertile platform for unveiling not only new natural product analogs with altered biological activity, but also for revealing new reactivity and selectivity hierarchies for embedded functional groups in complex environments. Motivated by these intersecting aims, we report site and stereoselective oxidation reactions of geldanamycin facilitated by aspartyl-peptide catalysts. Through the isolation and characterization of four new geldanamycin oxides, we discovered a synergistic effect between lead peptide-based catalysts and geldanamycin, resulting in an unexpected reaction pathway. Curiously, it seems unlikely that our discoveries would not have been possible absent the outer sphere interactions intrinsic to both the catalyst and the natural product. The result is a set of new “meta” catalytic reactions that deliver both unknown and previously incompletely characterized geldanamycin analogs. Enabled by the catalytic, site-selective epoxidation of geldanamycin, biological assays were carried out to document the bioactivities of the new compounds.<div><br></div>

scholarly journals Isolation and Characterization of Strain Exiguobacterium sp. KRL4, a Producer of Bioactive Secondary Metabolites from a Tibetan Glacier

2021 ◽  
Vol 9 (5) ◽  
pp. 890
Author(s):  
Pietro Tedesco ◽  
Fortunato Palma Esposito ◽  
Antonio Masino ◽  
Giovanni Andrea Vitale ◽  
Emiliana Tortorella ◽  
...  
Keyword(s):  
Phenotypic Analysis ◽  
Biological Assays ◽  
C Elegans ◽  
Isolation And Characterization ◽  
Wide Range ◽  
Protein Encoding ◽  
Nematocidal Activity ◽  
Extremophilic Microorganisms ◽  
Unique Source

Extremophilic microorganisms represent a unique source of novel natural products. Among them, cold adapted bacteria and particularly alpine microorganisms are still underexplored. Here, we describe the isolation and characterization of a novel Gram-positive, aerobic rod-shaped alpine bacterium (KRL4), isolated from sediments from the Karuola glacier in Tibet, China. Complete phenotypic analysis was performed revealing the great adaptability of the strain to a wide range of temperatures (5–40 °C), pHs (5.5–8.5), and salinities (0–15% w/v NaCl). Genome sequencing identified KRL4 as a member of the placeholder genus Exiguobacterium_A and annotation revealed that only half of the protein-encoding genes (1522 of 3079) could be assigned a putative function. An analysis of the secondary metabolite clusters revealed the presence of two uncharacterized phytoene synthase containing pathways and a novel siderophore pathway. Biological assays confirmed that the strain produces molecules with antioxidant and siderophore activities. Furthermore, intracellular extracts showed nematocidal activity towards C. elegans, suggesting that strain KRL4 is a source of anthelmintic compounds.

Site-selective phenol acylation mediated by thioacids via visible light photoredox catalysis

2018 ◽  
Vol 5 (8) ◽  
pp. 1312-1319 ◽  
Author(s):  
Lili Shi ◽  
Hongxin Liu ◽  
Luqiong Huo ◽  
Yaqian Dang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Visible Light ◽  
Natural Product ◽  
Hydroxyl Group ◽  
Photoredox Catalysis ◽  
Phenolic Esters ◽  
Site Selective

Site-selective phenol acylation mediated by thioacids via photoredox catalysis is described. This protocol provided facile access to an array of phenolic esters with exclusive acylation priority of phenol hydroxyl group to alcoholic one. Its utility was also demonstrated by the modification of biologically meaningful natural product.

scholarly journals A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 493 ◽  
Author(s):  
Li ◽  
Wang ◽  
Zhang ◽  
Zhang ◽  
Sajeevan ◽  
...  
Keyword(s):  
Small Molecules ◽  
Natural Product ◽  
Drug Targets ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Disease States ◽  
Clinical Drugs ◽  
Kinase Inhibitory Activity ◽  
New Compounds ◽  
Further Development

Protein kinases are validated drug targets for a number of therapeutic areas, as kinase deregulation is known to play an essential role in many disease states. Many investigated protein kinase inhibitors are natural product small molecules or their derivatives. Many marine-derived natural products from various marine sources, such as bacteria and cyanobacteria, fungi, animals, algae, soft corals, sponges, etc. have been found to have potent kinase inhibitory activity, or desirable pharmacophores for further development. This review covers the new compounds reported from the beginning of 2014 through the middle of 2019 as having been isolated from marine organisms and having potential therapeutic applications due to kinase inhibitory and associated bioactivities. Moreover, some existing clinical drugs based on marine-derived natural product scaffolds are also discussed.

Reaction Pathway Discrimination in Alkene Oxidation Reactions by Designed Ti‐Siloxy‐Polyoxometalates

ChemCatChem ◽  
2020 ◽  
Author(s):  
Teng Zhang ◽  
Albert Solé-Daura ◽  
Hugo Fouilloux ◽  
Josep M. Poblet ◽  
Anna Proust ◽  
...  
Keyword(s):  
Reaction Pathway ◽  
Oxidation Reactions ◽  
Alkene Oxidation

Parguerenes Revisited: New Brominated Diterpenes From the Southern Australian Marine Red Alga Laurencia Filiformis

1996 ◽  
Vol 49 (1) ◽  
pp. 19 ◽  
Author(s):  
SJ Rochfort ◽  
RJ Capon
Keyword(s):  
Natural Product ◽  
Biosynthetic Pathway ◽  
Spectroscopic Analysis ◽  
Red Alga ◽  
Biosynthetic Precursor ◽  
Chemical Correlation ◽  
New Compounds

Five new pargueranes, 15-bromoparguer-9(11)-ene-2,7,16,19-tetrol 2,7,16-triacetate (20), 15-bromoparguer-9(11)-ene-2,7,16-triol 2,7-diacetate (21), 15-bromoparguer-9(11)-ene-2,16-diol 2-acetate (22), 15-bromoparguer-9(11)-en-16-ol (23) and 15-bromoisoparguer-9(11)-en-16-ol (24), together with a plausible biosynthetic precursor, preparguerene (25), two known parguerenes , 15-bromoparguer-9(11)-ene-2,7,16,19-tetrol tetraacetate (4) and 15-bromoparguer-9(11)-ene-2,7,16-triol 2,16 diacetate (7), and the known algal metabolites (-)- aromadendrene (17), austradiol acetate (18) and austradiol diacetate (19), have been isolated from a collection of the southern Australian marine red alga Laurencia filiformis. The known synthetic parguerane 15-bromoparguer-9(11)-ene-2,7-16-triol triacetate (5) was also found for thefirst time as a natural product. In addition to securing the structures of new compounds by chemical correlation and detailed spectroscopic analysis, a lausible biosynthetic pathway has been proposed linking preparguerene, parguerene, isoparguerene and secoparguerene carbon skeletons.

scholarly journals Shushe Acids A-D from Ganoderma Applanatum

2017 ◽  
Vol 12 (3) ◽  
pp. 1934578X1701200
Author(s):  
Qi Luo ◽  
Yan-Jiao Zhang ◽  
Zhi-Qiang Shen ◽  
Peng Chen ◽  
Yong-Xian Cheng
Keyword(s):  
Succinic Acid ◽  
Natural Product ◽  
Gallic Acid ◽  
Spectroscopic Methods ◽  
Fruiting Bodies ◽  
Ganoderma Applanatum ◽  
Prevention And Treatment ◽  
New Compounds ◽  
Derivatives Of ◽  
Mcf 7

Ganoderma applanatum is a fungus used for the prevention and treatment of a variety of disorders in China. In the present study, four new compounds, named shushe acids A-D (1-4), were isolated from the fruiting bodies of this species. Their structures were identified on the basis of spectroscopic methods. Compounds 1-4 are all natural product hybrids composed of derivatives of gallic acid, glycerol and succinic acid. None of the four compounds showed activity against the MCF-7 cell line.

scholarly journals Isolation and Characterization of Two New Antimicrobial Acids from Quercus incana (Bluejack Oak)

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Rizwana Sarwar ◽  
Umar Farooq ◽  
Sadia Naz ◽  
Nadia Riaz ◽  
Syed Majid Bukhari ◽  
...  
Keyword(s):  
Ethyl Acetate Fraction ◽  
Structural Formula ◽  
2D Nmr ◽  
Spectroscopic Technique ◽  
Pentanoic Acid ◽  
One Dimensional ◽  
Isolation And Characterization ◽  
Nmr Techniques ◽  
New Compounds

Two new compounds [1-2] were purified from ethyl acetate fraction of Quercus incana. The structure of these compounds is mainly established by using advanced spectroscopic technique such as UV, IR, one-dimensional (ID) and two-dimensional (2D) NMR techniques, and EI mass. The structural formula was deduced to be 4-hydroxydecanoic acid [1] and 4-hydroxy-3-(hydroxymethyl) pentanoic acid [2]. Both isolated compounds were tested for their antimicrobial potential and showed promising antifungal activity against Aspergillus niger and Aspergillus flavus.

Isolation and Characterization of Two New Compounds from Genus Sonchus

2012 ◽  
Vol 5 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Zia Muhammad ◽  
Shabir Ahmad ◽  
Riaz Ullah ◽  
Farman Ullah ◽  
Saleem Jan
Keyword(s):  
Isolation And Characterization ◽  
New Compounds

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

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