ArticleJournal of the American Chemical Society2006
Total synthesis and evaluation of cytostatin, its C10-C11 diastereomers, and additional key analogues: impact on PP2A inhibition.
Article in Journal of the American Chemical Society, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 57 citations in OpenAlex.
- Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation.Nature communications · 2026Article
- Enantioselective β-C(spJournal of the American Chemical Society · 2025Article
- Synthesis of the C28-C41 Side Chain of (Proposed) Neaumycin B: A Contiguous Stereohextet.Organic letters · 2023Article
- Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition.Beilstein journal of organic chemistry · 2022Article
- The potent protein phosphatase 2A inhibitors aminocytostatins: new derivatives of cytostatin.The Journal of antibiotics · 2021Article
- The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C.Molecular cancer therapeutics · 2019Article
- Inhibitors of Serine/Threonine Protein Phosphatases: Biochemical and Structural Studies Provide Insight for Further Development.Current medicinal chemistry · 2019Review
- The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry-Biology Interface.The Journal of organic chemistry · 2017Article
- Formation of α-chiral centers by asymmetric β-C(sp3)-H arylation, alkenylation, and alkynylation.Science (New York, N.Y.) · 2017Article
- Synthetic Strategies Employed for the Construction of Fostriecin and Related Natural Products.Chemical reviews · 2016Review
- A Highly Convergent Total Synthesis of Leustroducsin B.Journal of the American Chemical Society · 2015Article
- Suppression of Ser/Thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death.Molecular cancer research : MCR · 2013Article
- De novo synthesis of natural products via the asymmetric hydration of polyenes.Chemical communications (Cambridge, England) · 2011Review
- Total synthesis and evaluation of phostriecin and key structural analogues.The Journal of organic chemistry · 2010Article
- Enantioselective hydroformylation of N-vinyl carboxamides, allyl carbamates, and allyl ethers using chiral diazaphospholane ligands.Journal of the American Chemical Society · 2010Article
- Total synthesis of fostriecin: via a regio- and stereoselective polyene hydration, oxidation, and hydroboration sequence.Organic letters · 2010Article
- Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis.Cancer science · 2010Article
- Total synthesis, assignment of the relative and absolute stereochemistry, and structural reassignment of phostriecin (aka Sultriecin).Journal of the American Chemical Society · 2010Article
- Structure-activity relationship studies of fostriecin, cytostatin, and key analogs, with PP1, PP2A, PP5, and( beta12-beta13)-chimeras (PP1/PP2A and PP5/PP2A), provide further insight into the inhibitory actions of fostriecin family inhibitors.The Journal of pharmacology and experimental therapeutics · 2009Article
- cis-Delta(2,3)-double bond of phoslactomycins is generated by a post-PKS tailoring enzyme.Journal of the American Chemical Society · 2008Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The total synthesis of cytostatin, an antitumor agent belonging to the fostriecin family of natural products, is described in full detail. The convergent approach relied on a key epoxide-opening reaction to join the two stereotriad units and a single-step late-stage stereoselective installation of the sensitive (Z,Z,E)-triene through a beta-chelation-controlled nucleophilic addition. The synthetic route provided rapid access to the C4-C6 stereoisomers of the cytostatin lactone, which were prepared and used to define the C4-C6 relative stereochemistry of the natural product. In addition to the natural product, each of the C10-C11 diastereomers of cytostatin was divergently prepared (11 steps from key convergence step) by this route and used to unequivocally confirm the relative and absolute stereochemistry of cytostatin. Each of the cytostatin diastereomers exhibited a reduced activity toward inhibition of PP2A (>100-fold), demonstrating the importance of the presence and stereochemistry of the C10-methyl and C11-hydroxy groups for potent PP2A inhibition. Extensions of the studies provided dephosphocytostatin, sulfocytostatin (a key analogue related to the natural product sultriecin), 11-deshydroxycytostatin, and an analogue lacking the entire C12-C18 (Z,Z,E)-triene segment, which were used to define the magnitude of the C9-phosphate (>4000-fold), C11-alcohol (250-fold), and triene (220-fold) contribution to PP2A inhibition. A model of cytostatin bound to the active site of PP2A is presented, compared to that of fostriecin, which is also presented in detail for the first time, and used to provide insights into the role of the key substituents. Notably, the alpha,beta unsaturated lactone of cytostatin, like that of fostriecin, is projected to serve as a key electrophile, providing a covalent adduct with Cys269 unique to PP2A, contributing to its potency (> or =200-fold for fostriecin) and accounting for its selectivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.