108149-62-8Relevant articles and documents
MEAYAMYCIN ANALOGUES AND METHODS OF USE
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Page/Page column 6-7; 18, (2021/10/15)
Compounds according to formula (I), where R is as defined herein, have anti-cancer properties.
Total Synthesis of Meayamycin and O-Acyl Analogues
Boger, Dale L.,Chanda, Prem B.,Chowdari, Naidu S.,Gangwar, Sanjeev,Gartshore, Christopher,Momirov, Jelena,Sarkar, Anindya,Tadano, Shinji,Vite, Gregory D.,Zhang, Qian
supporting information, (2020/11/18)
A short, scalable total synthesis of meayamycin is described by an approach that entails a longest linear sequence of 12 steps (22 steps overall) from commercially available chiral pool materials (ethyl l-lactate, BocNH-Thr-OH, and d-ribose) and introduces the most straightforward preparation of the right-hand subunit detailed to date. The use of the approach in the divergent synthesis of a representative series of O-acyl analogues is exemplified.
THAILANSTATIN ANALOGS
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Paragraph 0330; 0331, (2019/04/05)
The invention provides novel cytotoxic compounds and cytotoxic conjugates comprising these cytotoxic compounds and cell-binding agents. More specifically, this invention relates to novel thailanstatin A analogs, useful as cytotoxic small molecule toxins i
Total syntheses of linear polythiazole/oxazole plantazolicin A and its biosynthetic precursor plantazolicin B
Wilson, Zoe E.,Fenner, Sabine,Ley, Steven V.
supporting information, p. 1284 - 1288 (2015/01/30)
Plantazolicin A, a linear decacyclic natural product, exhibits desirable selective activity against the causative agent of anthrax toxicity. The total synthesis of plantazolicin A and its biosynthetic precursor plantazolicin B was successfully achieved by an efficient, unified, and highly convergent route featuring dicyclizations to form 2,4-concatenated oxazoles and the mild synthesis of thiazoles from natural amino acids. This report represents the first synthesis of plantazolicin B and includes the first complete characterization data for both natural products.
From the Feist-Bénary reaction to organocatalytic domino Michael-alkylation reactions: Asymmetric synthesis of 3(2H)-furanones
Dou, Xiaowei,Han, Xiaoyu,Lu, Yixin
supporting information; experimental part, p. 85 - 89 (2012/02/04)
It all adds up! A modified Feist-Bénary reaction employing a domino Michael-alkylation sequence was designed for the enantioselective synthesis of 3(2H)-furanones. L-Threonine-derived tertiary amine/thiourea catalysts were prepared for the first time; such catalysts promoted the designed domino Michael-alkylation reactions in a highly enantioselective manner (see scheme). Copyright
SYNTHESIS OF FR901464 AND ANALOGS WITH ANTITUMOR ACTIVITY
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Page/Page column 11, (2008/06/13)
The present invention provides novel analogs of FR901464, as well as an improved methodology for preparing FR901464 and its analogs. These compounds display an anti-cancer activity and are candidates for therapies against a number of disease states associ
An improved method for culturing Streptomyces sahachiroi: Biosynthetic origin of the enol fragment of azinomycin B
Kelly, Gilbert T.,Sharma, Vasudha,Watanabe, Coran M.H.
, p. 4 - 15 (2008/09/21)
Azinomycin B is an environmental DNA crosslinking agent produced by the soil microorganism Streptomyces sahachiroi. While the agent displays potent cytotoxic activities against leukemic cell lines and animal mouse models, the lack of a consistent supply of the natural product has hampered detailed biological investigations on the compound, including its mode of action and biosynthesis. We report here a significant methodological improvement in the culturing of the bacterium, which allows reliable and steady production of the natural product in good yields. The key experimental step involves the culturing of the strain on dehydrated plates, followed by the generation of a two-stage starter culture and subsequent fermentation of the strain under nutrient-starved conditions. We illustrate use of this culture system by investigating the formation of the enol fragment of the molecule in isotopic labeling experiments with threonine and several advanced precursors (β-ketoamino acid 3, β-hydroxyamino aldehyde 4, and β-ketoaminoaldehyde 5). The results unequivocally show that threonine is the most advanced precursor accepted by the NRPS (non-ribosomal peptidyl synthetase) machinery for final processing and construction of the enol moiety of the natural product.
Total syntheses, fragmentation studies, and antitumor/antiproliferative activities of FR901464 and its low picomolar analogue
Albert, Brian J.,Sivaramakrishnan, Ananthapadmanabhan,Naka, Tadaatsu,Czaicki, Nancy L.,Koide, Kazunori
, p. 2648 - 2659 (2007/10/03)
FR901464 is a potent anticancer natural product that lowers the mRNA levels of oncogenes and tumor suppressor genes. In this article, we report a convergent enantioselective synthesis of FR901464, which was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6-C7 olefin without the use of protecting groups as the final step. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 Stereocenter, a mild and chemoselective Red-Al reduction, a reagent-controlled stereoselective Mislow-Evans-type [2,3]-sigmatropic rearrangement to install the C5 Stereocenter, a Carreira asymmetric alkynylation to generate the C4′ stereocenter, and a highly efficient ring-closing metathesis-allylic oxidation sequence to form an unsaturated lactone. The decomposition pathways of FR901464's right fragment were studied under physiologically relevant conditions. Facile epoxide opening by β-elimination gave two enones, one of which could undergo dehydration via its hemiketal to form a furan. To prevent this decomposition pathway, a right fragment was rationally designed and synthesized. This analogue was 12 times more stable than the right fragment of the natural product. Using this more stable right fragment analogue, an FR901464 analogue, meayamycin, was prepared in 13 linear steps. The inhibitions of human breast cancer MCF-7 cell proliferation by synthetic FR901464 and meayamycin were studied, and the GI50 values for these compounds were determined to be 1.1 nM and 10 pM, respectively. Thus, meayamycin is among the most potent anticancer small molecules that do not bind to either DNA or microtubule.
Scope and limitations of the alkylidene carbene 1,5-CH insertion reactions of α-amino acid-derived substrates
Mapitse, Renameditswe,Hayes, Christopher J
, p. 3541 - 3542 (2007/10/03)
A range of α-amino acid-derived cyclisation precursors were synthesised from suitably protected α-amino esters, via a Dibal-H/Wittig/catalytic hydrogenation strategy and each of these was subjected to alkylidene carbene-forming conditions (lithio(trimethy
4-Alkenyl- and 4-alkynyloxindoles
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, (2008/06/13)
Disclosed are novel 4-alkenyl- and 4-alkynyl oxindoles having the formula and the pharmaceutically acceptable salts thereof, wherein R1, R2, R3, a, b, and X are as defined herein. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast and colon tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I and II as well as intermediates useful in the preparation of the compounds of formula I and II.
