Total Synthesis of the Antitumor Natural Product Polycarcin V and Evaluation of Its DNA Binding Profile

Cai, Xiao; Ng, Kevin; Panesar, Harmanpreet; Moon, Seong-Jin; Paredes, M. D.; Ishida, Keishi; Hertweck, Christian; Minehan, Thomas G.

doi:10.1021/ol501095w

Cited by 38 publications

(30 citation statements)

References 47 publications

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“…[1a, 8] PV offered the possibility of enzymatic O -methylation of the sugar moiety, since many L-rhamnose- O -methyltransferases are known. Unlike the rare sugar D-fucofuranose, an L-rhamnopyranose moiety, usually as mono, di-, per- O -methylated derivatives are found commonly in polyketides, for example in the steffimycin, elloramycin and spinosyn pathways (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

“…[3] Since PV is the natural by-product of the GV producer S. polyformus , this compound could be easily produced to serve as a control standard. For these reasons we chose PV as an alternative to GV for initial SAR studies regarding the sugar moiety, [8a] expecting some insight into the importance of the three hydroxyl groups of the sugar, which could be important to design better soluble GV-type analogues.…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V, a Gilvocarcin‐Type Antitumor Agent

et al. 2014

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Polycarcin V, a polyketide natural product of Streptomyces polyformus, was chosen to study structure-activity-relationships of the gilvocarcin group of antitumor antibiotics, because of a similar chemical structure and comparable bioactivity with gilvocarcin V, the principle compound of this group, and the feasibility of enzymatic modifications of its sugar moiety by auxiliary O-methyltransferases. Such enzymes were used to modify the interaction of the drug with histone H3, the biological target that interacts with the sugar moiety. Cytotoxicity assays revealed that a free 2’-OH group of the sugar moiety is essential to maintain the bioactivity of polycarcin V, apparently an important H-bond donor for the interaction with histone H3, while converting 3'-OH into an OCH3 group improved the bioactivity. Bis-methylated polycarcin derivatives revealed weaker activity than the parent compound, indicating that at least two H-bond donors in the sugar are necessary for optimal binding.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V, a Gilvocarcin‐Type Antitumor Agent

et al. 2014

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“…The regioselective formation of C2‐glycosylated product probably proceeds via the O‐ to C‐glycoside rearrangement sequence that was previously proposed by Suzuki and co‐workers. [ 47‐48 ] In contrast, C4‐glycosylated products may only be formed via Friedel‐Crafts type C4‐glycosylation, which is sterically favored comparing to C2‐glycosylation. In this process, 4 Å MS blocked the removal of i ‐Pr group of 136 by SnCl 4 and thus presumably increased the proportion of the Friedel‐Crafts reaction to afford better yield.…”

Section: Function‐oriented Synthesis In Drug Discoverymentioning

confidence: 99%

Function‐Oriented Natural Product Synthesis

Chen

Lei

2021

Chin. J. Chem.

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What is the most favorite and original chemistry developed in your research group? By far the most original and groundbreaking work we have done is the discovery of the first naturally occurring TRUE Diels-Alderase which shows tremendous synthetic potential in biocatalysis for efficiently making structurally complex and bioactive molecules. How do you get into this specific field? Could you please share some experiences with our readers? I have a great passion in synthetic chemistry, and I am always fascinated by making organic molecules that may help us explore new biology and develop medicine for human diseases. Therefore, my research programs are relatively broad, spanning from natural product synthesis, chemical biology, synthetic biology, biocatalysis to drug discovery. What is the most important personality for scientific research? In my personal opinion, curiosity, ambition, and dedication are the most important personalities for scientific research. What is your favorite journal(s)? My favorite journals are: 1) Cell, when you read a Cell paper, you can get a full story of the original discovery and understand the detailed logic on how the research is planned and conducted; 2) Accounts of Chemical Research, this journal provides a short review on how a chemist establishes a specific new research field, very inspiring! What's your hobbies? I love many sports, soccer, American football, basketball, etc. I am also good at Seal Cutting, one of the four major traditional Chinese arts. If you have anything else to tell our readers, please feel free to do so. I would like to share one advice with the young scientists who just start their independent research career: BE DIFFERENT from your Ph.D. and Postdoc advisors, try to establish your own research direction! It's always easy to quickly get paper published when you take advantage of your advisor's research system, but it's very challenging to establish your own reputation and prove your originality in this way.

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“…Polysubstituted naphthols have found wide applications in organic synthesis and drug development (Scheme 1). [1,2] For instance, BINOLs and naphthol derived salen-type ligands are extensively applied in asymmetric catalysis. [3,4] A number of biologically active natural products, such as nigerone, [5] gossypols, [6] and kedarcidin, [7] possess a 2-naphthol backbone.…”

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confidence: 99%

“…[c] With 10 mol% of Pd(TFA) 2 . [d] [1,3]dioxole-derived substrate 1 h was employed, only a moderate yield was achieved (2 h, 46% yield). Subsequently, a series of electron-withdrawing substituents, including F, Cl, and NO 2 at different positions of the aryl ring, were also studied.…”

mentioning

confidence: 99%

Synthesis of Polysubstituted 2‐Naphthols by Palladium‐Catalyzed Intramolecular Arylation/Aromatization Cascade

et al. 2020

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A palladium‐catalyzed intramolecular α‐arylation and defluorinative aromatization strategy for the synthesis of polysubstituted 2‐naphthols is reported. With ortho‐bromobenzyl‐substituted α‐fluoroketones as the substrates and palladium acetate/triphenylphosphine as the catalyst, this method features good functional group tolerance, readily available catalyst and starting materials, and high yields. The applications of the strategy are demonstrated by the synthesis of useful building blocks, such as naphtha[2,3‐b]furan, naphthol AS‐D, and ligands/catalysts.

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Total Synthesis of the Antitumor Natural Product Polycarcin V and Evaluation of Its DNA Binding Profile

Cited by 38 publications

References 47 publications

Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V, a Gilvocarcin‐Type Antitumor Agent

Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V, a Gilvocarcin‐Type Antitumor Agent

Function‐Oriented Natural Product Synthesis

Synthesis of Polysubstituted 2‐Naphthols by Palladium‐Catalyzed Intramolecular Arylation/Aromatization Cascade

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