Total syntheses of spirocyclic PKS-NRPS-based fungal metabolites

2018 ◽  
Vol 54 (50) ◽  
pp. 6750-6758 ◽  
Author(s):  
Deokhee Jo ◽  
Sunkyu Han

We present the isolations, the biosynthetic studies, the biological activities, and the comprehensive description of all reported total syntheses of spirocyclic PKS-NRPS-based fungal natural products.

2020 ◽  
Vol 27 (8) ◽  
pp. 1243-1307 ◽  
Author(s):  
Dario Matulja ◽  
Karlo Wittine ◽  
Nela Malatesti ◽  
Sylvain Laclef ◽  
Maris Turks ◽  
...  

This review covers recent literature from 2012-2019 concerning 170 marine natural products and their semisynthetic analogues with strong anticancer biological activities. Reports that shed light on cellular and molecular mechanisms and biological functions of these compounds, thus advancing the understanding in cancer biology are also included. Biosynthetic studies and total syntheses, which have provided access to derivatives and have contributed to the proper structure or stereochemistry elucidation or revision are mentioned. The natural compounds isolated from marine organisms are divided into nine groups, namely: alkaloids, sterols and steroids, glycosides, terpenes and terpenoids, macrolides, polypeptides, quinones, phenols and polyphenols, and miscellaneous products. An emphasis is placed on several drugs originating from marine natural products that have already been marketed or are currently in clinical trials.


2016 ◽  
Vol 113 (13) ◽  
pp. 3521-3526 ◽  
Author(s):  
Wei Ding ◽  
Wan-Qiu Liu ◽  
Youli Jia ◽  
Yongzhen Li ◽  
Wilfred A. van der Donk ◽  
...  

Production of ribosomally synthesized and posttranslationally modified peptides (RiPPs) has rarely been reported in fungi, even though organisms of this kingdom have a long history as a prolific source of natural products. Here we report an investigation of the phomopsins, antimitotic mycotoxins. We show that phomopsin is a fungal RiPP and demonstrate the widespread presence of a pathway for the biosynthesis of a family of fungal cyclic RiPPs, which we term dikaritins. We characterize PhomM as an S-adenosylmethionine–dependent α-N-methyltransferase that converts phomopsin A to anN,N-dimethylated congener (phomopsin E), and show that the methyltransferases involved in dikaritin biosynthesis have evolved differently and likely have broad substrate specificities. Genome mining studies identified eight previously unknown dikaritins in different strains, highlighting the untapped capacity of RiPP biosynthesis in fungi and setting the stage for investigating the biological activities and unknown biosynthetic transformations of this family of fungal natural products.


Science ◽  
2020 ◽  
Vol 368 (6494) ◽  
pp. 1007-1011 ◽  
Author(s):  
Barry M. Trost ◽  
Youliang Wang ◽  
Andreas K. Buckl ◽  
Zhongxing Huang ◽  
Minh H. Nguyen ◽  
...  

Bryostatins are a family of 21 complex marine natural products with a wide range of potent biological activities. Among all the 21 bryostatins, bryostatin 3 is structurally the most complex. Whereas nine total syntheses of bryostatins have been achieved to date, bryostatin 3 has only been targeted once and required the highest number of steps to synthesize (43 steps in the longest linear sequence and 88 total steps). Here, we report a concise total synthesis of bryostatin 3 using 22 steps in the longest linear sequence and 31 total steps through a highly convergent synthetic plan by the use of highly atom-economical and chemoselective transformations in which alkynes played a major role in reducing step count.


1995 ◽  
Vol 73 (12) ◽  
pp. 2119-2125 ◽  
Author(s):  
Albert K. Amegadzie ◽  
William A. Ayer ◽  
Lynne. Sigler

The metabolites of the wood rot decay fungus Sistotremaraduloides (P. Karst) Donk have been investigated and a new type of norpentaketide has been discovered. The compounds sistodiolynne (1), sistolynone (5), and sistopyrone (6) represent new carbon skeletons among natural products. The compounds are very unstable and readily polymerize in the presence of air to give black insoluble material. It has been shown by 13C NMR labelling experiments that they arise from five acetate units, and that a methyl carbon of one of the acetate units is lost during the biosynthesis. The structures were determined by spectroscopy methods, mainly NMR, and the absolute configuration of sistodiolynne was established by circular dichroism methods. Keywords: fungal metabolites, Sistotremaraduloides, norpentaketides, biosynthetic studies, polyacetylenes.


Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3912 ◽  
Author(s):  
Guo-Fei Qin ◽  
Hong-Bao Liang ◽  
Wen-Xiu Liu ◽  
Feng Zhu ◽  
Ping-Lin Li ◽  
...  

Sesquiterpenoids constitute a marvelously varied group of natural products that feature a vast array of molecular architectures. Among them, the unusual bicyclo [6.3.0] undecane sesquiterpenoids are one of the most representative. To date, only approximately 42 naturally occurring compounds with this unique scaffold, which can be classified into seven different groups, have been reported. As the first-found member of each type, dactylol, asteriscanolide, dumortenol, toxicodenane C, and capillosanane S are characteristic of the four methyl groups on the five-eight-membered ring system. Only 11-hydroxyjasionone and sinuketal decorate the core with an isopropyl group. These natural products exhibit a wide range of bioactivities, including antifouling, anti-inflammatory, immune suppression, cytotoxic, antimutagenic, antiplasmodial, and antiviral activities. It was noted that some total syntheses of precapnellane-sesquiterpenoids (dactylol, poitediol, precapnelladiene), asteriscanolide, and 11-hydroxyjasionone have been achieved, because their cyclooctanoid core represents an important target for the development of synthetic strategies to prepare eight-membered ring-containing compounds. This review focuses on these natural sesquiterpenoids and their biological activities and synthesis, and aims to provide a foundation for further research of these interesting compounds.


MedChemComm ◽  
2015 ◽  
Vol 6 (3) ◽  
pp. 425-430 ◽  
Author(s):  
Michio Sato ◽  
Haruka Yamada ◽  
Kinya Hotta ◽  
Kenji Watanabe

Since fungal natural products biosynthesized by polyketide synthases frequently exhibit useful biological activities, identifying and understanding the mechanism of biosynthetic steps taken by PKSs are of great interest.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
T Thorskov Bladt ◽  
S Kildgaard ◽  
P Boldsen Knudsen ◽  
C Held Gotfredsen ◽  
C Dürr ◽  
...  

2020 ◽  
Vol 24 (4) ◽  
pp. 354-401 ◽  
Author(s):  
Keisham S. Singh

Marine natural products (MNPs) containing pyrone rings have been isolated from numerous marine organisms, and also produced by marine fungi and bacteria, particularly, actinomycetes. They constitute a versatile structure unit of bioactive natural products that exhibit various biological activities such as antibiotic, antifungal, cytotoxic, neurotoxic, phytotoxic and anti-tyrosinase. The two structure isomers of pyrone ring are γ- pyrone and α-pyrone. In terms of chemical motif, γ-pyrone is the vinologous form of α- pyrone which possesses a lactone ring. Actinomycete bacteria are responsible for the production of several α-pyrone compounds such as elijopyrones A-D, salinipyrones and violapyrones etc. to name a few. A class of pyrone metabolites, polypropionates which have fascinating carbon skeleton, is primarily produced by marine molluscs. Interestingly, some of the pyrone polytketides which are found in cone snails are actually synthesized by actinomycete bacteria. Several pyrone derivatives have been obtained from marine fungi such as Aspergillums flavus, Altenaria sp., etc. The γ-pyrone derivative namely, kojic acid obtained from Aspergillus fungus has high commercial demand and finds various applications. Kojic acid and its derivative displayed inhibition of tyrosinase activity and, it is also extensively used as a ligand in coordination chemistry. Owing to their commercial and biological significance, the synthesis of pyrone containing compounds has been given attention over the past years. Few reviews on the total synthesis of pyrone containing natural products namely, polypropionate metabolites have been reported. However, these reviews skipped other marine pyrone metabolites and also omitted discussion on isolation and detailed biological activities. This review presents a brief account of the isolation of marine metabolites containing a pyrone ring and their reported bio-activities. Further, the review covers the synthesis of marine pyrone metabolites such as cyercene-A, placidenes, onchitriol-I, onchitriol-II, crispatene, photodeoxytrichidione, (-) membrenone-C, lihualide-B, macrocyclic enol ethers and auripyrones-A & B.


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