- Diols as Building Blocks in Solid-Phase Synthesis of Polyamine Toxins by Fukuyama-Mitsunobu Alkylation
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Philanthotoxin-433 (PhTX-433) is a polyamine wasp toxin that antagonizes certain ionotropic receptors. In the present work three analogues of PhTX-433 were synthesized in good overall yields (27-31%) employing a Fukuyama-Mitsunobu strategy on solid phase.
- Olsen, Christian A.,Witt, Matthias,Jaroszewski, Jerzy W.,Franzyk, Henrik
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Read Online
- Biosynthetic products from a nearshore-derived gram-negative bacterium enable reassessment of the kailuin depsipeptides
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Sampling of California nearshore sediments resulted in the isolation of a Gram-negative bacterium, Photobacterium halotolerans, capable of producing unusual biosynthetic products. Liquid culture in artificial seawater-based media provided cyclic depsipeptides including four known compounds, kailuins B-E (2-5), and two new analogues, kailuins G and H (7 and 8). The structures of the new and known compounds were confirmed through extensive spectroscopic and Marfeys analyses. During the course of these studies, a correction was made to the previously reported double-bond geometry of kailuin D (4). Additionally, through the application of a combination of derivatization with Moshers reagent and extensive 13C NMR shift analysis, the previously unassigned chiral center at position C-3 of the β-acyloxy group of all compounds was determined. To evaluate bioactivity and structure-activity relationships, the kailuin core (13) and kailuin lactam (14) were prepared by chiral synthesis using an Fmoc solid-phase peptide strategy followed by solution-phase cyclization. All isolated compounds and synthetic cores were assayed for solid tumor cell cytotoxicity and showed only minimal activity, contrary to other published reports. Additional phenotypic screenings were done on 4 and 5, with little evidence of activity.
- Theodore, Christine M.,Lorig-Roach, Nicholas,Still, Patrick C.,Johnson, Tyler A.,Dra?kovi?, Marija,Schwochert, Joshua A.,Naphen, Cassandra N.,Crews, Mitchell S.,Barker, Simone A.,Valeriote, Frederick A.,Lokey, R. Scott,Crews, Phillip
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Read Online
- Total stereocontrolled synthesis of a novel pyrrolizidine iminosugar
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Herein we describe a versatile approach to the pyrrolizidine alkaloids skeleton by tailoring our original strategy already used for the pyrrolidine iminosugars synthesis. The key steps are the regio- and stereoselective azidolysis of the suitable chiral v
- De Angelis, Martina,Primitivo, Ludovica,Lizzio, Federica,Agostinelli, Sonia,Sappino, Carla,Ben Romdan, Ilaria,Bonanni, Luciano,D'Annibale, Andrea,Antonioletti, Roberto,Ricelli, Alessandra,Righi, Giuliana
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- Studies toward the Synthesis of an Oxazole-Based Analog of (-)-Zampanolide
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Studies are described toward the synthesis of an oxazole-based analog of (-)-zampanolide (2). Construction of (-)-dactylolide analog 22 was achieved via alcohol 5 and acid 4 through esterification and Horner-Wadsworth-Emmons (HWE)-based macrocyclization; however, attempts to attach (Z,E)-sorbamide to 22 proved unsuccessful. The C(8)-C(9) double bond of the macrocycle was prone to migration into conjugation with the oxazole ring, which may generally limit the usefulness of zampanolide analogs with aromatic moieties as tetrahydropyran replacements.
- Bold, Christian P.,Klaus, Cindy,Pfeiffer, Bernhard,Schurmann, Jasmine,Lombardi, Rafael,Lucena-Agell, Daniel,Diaz, J. Fernando,Altmann, Karl-Heinz
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supporting information
p. 2238 - 2242
(2021/04/05)
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- Large-Scale Synthesis of Eldecalcitol
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Industrial-scale synthesis of eldecalcitol is described. AA highly diastereoselective epoxidation of p-methoxybenzyl (PMB) protected dienol at room temperature provides the key epoxide intermediate with a secondary hydroxyl group, which is alkylated with a triflate to set up all of the subunits at the C-1, C-2, and C-3 positions of the A-ring fragment. Selective protecting group manipulation followed by palladium-catalyzed cyclization then provides the A-ring synthon. The C/D-ring fragment is obtained by (1) direct C-H hydroxylation of Grundman's ketone using in situ prepared trifluoropropanone dioxirane and (2) protection. Finally, the coupling of the A-ring with the C/D-ring fragment, global deprotection, and recrystallization provide the highly crystalline eldecalcitol.
- Moon, Hyung Wook,Lee, Seung Jong,Park, Seong Hu,Jung, Se Gyo,Jung, In A.,Seol, Chang Hun,Kim, Seung Woo,Lee, Seon Mi,Gangganna, Bogonda,Park, Seokhwi,Lee, Kee-Young,Oh, Chang-Young,Song, Juyoung,Jung, Jaehun,Heo, Ji Soo,Lee, Kang Hee,Kim, Hae Sol,Lee, Won Taek,Baek, Areum,Shin, Hyunik
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supporting information
p. 98 - 107
(2021/01/09)
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- Synthesis of Optically Active Maresin 2 and Maresin 2 n-3 DPA
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Maresins are among the most potent antiinflammatory lipid metabolites. We report stereoselective syntheses of maresin 2 and maresin 2 n-3 DPA. The anti -diol was constructed through epoxide ring opening of an optically active β,γ-epoxy aldehyde, synthesized in situ by Swern oxidation of the corresponding alcohol. Finally, the target compounds were synthesized through a Sonogashira coupling of a C9-C22 iodide and methyl (Z)-oct-4-en-7-ynoate or methyl oct-7-ynoate, respectively.
- Ogawa, Narihito,Amano, Takahito,Kobayashi, Yuichi
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supporting information
p. 295 - 298
(2020/11/18)
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- Synthesis of the analogs of plocabulin and their preliminary structure-activity relationship study
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Plocabulin, a marine natural polyketide isolated from the sponge Lithoplocamia lithistoides, is a novel and potent microtubule-destabilizing agent. Guided by the reported binding mode, several new analogs of plocabulin have been designed through removing
- Wang, Leiming,Li, Xin,Cui, Hong,Lei, Xinsheng,Liu, Hongchun,Wang, Quanrui,Li, Yingxia
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supporting information
(2021/09/28)
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
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Paragraph 0522-0524
(2021/04/23)
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- The Biosynthetic Gene Cluster for Sestermobaraenes—Discovery of a Geranylfarnesyl Diphosphate Synthase and a Multiproduct Sesterterpene Synthase from Streptomyces mobaraensis
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A biosynthetic gene cluster from Streptomyces mobaraensis encoding the first cases of a bacterial geranylfarnesyl diphosphate synthase and a type I sesterterpene synthase was identified. The structures of seven sesterterpenes produced by these enzymes were elucidated, including their absolute configurations. The enzyme mechanism of the sesterterpene synthase was investigated by extensive isotope labeling experiments.
- Dickschat, Jeroen S.,Hou, Anwei
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supporting information
p. 19961 - 19965
(2020/09/02)
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- NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
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Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a
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Paragraph 0362
(2020/12/29)
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- Total Synthesis of (-)-Mitrephorone A Enabled by Stereoselective Nitrile Oxide Cycloaddition and Tetrasubstituted Olefin Synthesis
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A highly enantioselective and diastereoselective total synthesis of the diterpenoid (-)-mitrephorone A is presented. Key to the synthesis are stereocontrolled 1,4-semihydrogenation of a 1,3-diene to a tetrasubstituted double bond, enzyme-catalyzed malonat
- Carreira, Erick M.,Richter, Matthieu J. R.,Schneider, Michael
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supporting information
p. 17802 - 17809
(2020/11/02)
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- A fluorine scan on the Zn2+-binding thiolate side chain of HDAC inhibitor largazole: Synthesis, biological evaluation, and molecular modeling
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Based on the unique role of a common unit in a family of sulfur-containing natural histone deacetylases (HDACs) inhibitors, we have chosen largazole as an example of these inhibitors and adopted a “fluorine scan” strategy towards modification of this common unit. Thus a set of fluoro largazole analogues has been designed, synthesized and evaluated in enzymatic as well as cellular assays. The preliminary results indicate that introduction of fluorine at the various position of the unit has an important impact on the activity and selectivity of HDACs. Unlike other modifications which often led to significant reduction or complete loss of activity as reported in the literature, most of these fluoro thiols have displayed comparable or enhanced activity and selectivity in enzymatic assays. Two of the sulfhydryl esters have also exhibited excellent inhibitory activity in cellular assays with a few selected cell lines. The C19-fluorinated analogue has been further studied by immunoblot analysis, confirming that it is a potent selective class I HDAC inhibitor and supporting that the potent cellular antiproliferative activity is due to HDAC inhibition. The molecular docking study reveals that introducing fluorine at the C19 position does not change the original interactions, but might have made a subtle change in binding conformation, resulting in an obvious improvement in activity.
- Zhang, Bingbing,Liu,Gao, Dingding,Yu, Xiaolin,Wang, Jinlei,Lei, Xinsheng
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supporting information
(2019/09/10)
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- Deletion of the C26 Methyl Substituent from the Bryostatin Analogue Merle 23 Has Negligible Impact on Its Biological Profile and Potency
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Important strides are being made in understanding the effects of structural features of bryostatin 1, a candidate therapeutic agent for cancer and dementia, in conferring its potency toward protein kinase C and the unique spectrum of biological responses that it induces. A critical pharmacophoric element in bryostatin 1 is the secondary hydroxy group at the C26 position, with a corresponding primary hydroxy group playing an analogous role in binding of phorbol esters to protein kinase C. Herein, we describe the synthesis of a bryostatin homologue in which the C26 hydroxy group is primary, as it is in the phorbol esters, and show that its biological activity is almost indistinguishable from that of the corresponding compound with a secondary hydroxy group.
- Zhao, Xiguang,Kedei, Noemi,Michalowski, Alexandra,Lewin, Nancy E.,Keck, Gary E.,Blumberg, Peter M.
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p. 1049 - 1059
(2018/05/31)
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- NiH-Catalyzed Reductive Relay Hydroalkylation: A Strategy for the Remote C(sp3)?H Alkylation of Alkenes
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The terminal-selective, remote C(sp3)?H alkylation of alkenes was achieved by a relay process combining NiH-catalyzed hydrometalation, chain walking, and alkylation. This method enables the construction of unfunctionalized C(sp3)?C(sp3) bonds under mild conditions from two simple feedstock chemicals, namely olefins and alkyl halides. The practical value of this transformation is further demonstrated by the large-scale and regioconvergent alkylation of isomeric mixtures of olefins at low catalyst loadings.
- Zhou, Fang,Zhu, Jin,Zhang, Yao,Zhu, Shaolin
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supporting information
p. 4058 - 4062
(2018/03/21)
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- A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions
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A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.
- Huy, Peter H.,Filbrich, Isabel
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supporting information
p. 7410 - 7416
(2018/04/30)
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- Process for Preparing Eldecalcitol and Intermediate Therefor
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The present invention relates to an eldecalcitol manufacturing method and an intermediate product therefor. According to an embodiment of the present invention, the eldecalcitol manufacturing method comprises: a step of obtaining a compound of chemical formula 3; a step of obtaining a compound of chemical formula 4; and a step of applying an allyl alcohol group of the compound of the chemical formula 4 to an asymmetric epoxidation reaction. According to the present invention, the eldecalcitol manufacturing method and the intermediate product therefor can manufacture eldecalcitol without a complex manufacturing process.COPYRIGHT KIPO 2018
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Paragraph 0231; 0232
(2018/06/26)
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- Dihydropyrone compound and preparation method and purpose thereof
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The invention belongs to the field of drug synthesis and relates to a novel dihydropyrone compound and a preparation method and a purpose thereof. The chemical formula of the dihydropyrone compound isshown in the following general formula I, biological ex
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Paragraph 0079; 0080; 0081
(2018/10/01)
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- Enantioselective NiH/Pmrox-Catalyzed 1,2-Reduction of α,β-Unsaturated Ketones
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The enantioselective 1,2-reduction of α,β-unsaturated ketones was achieved using a NiH catalyst in the presence of pinacolborane. This mild process represents a general method to access a wide variety of structurally diverse α-chiral allylic alcohols in excellent yields and enantioselectivity, as well as very high levels of ambidoselectivity for 1,2- over 1,4-reduction. Furthermore, for reactions on a 10 mmol scale, catalyst loadings as low as 0.5 mol % could be employed to deliver product without any detrimental effect on the yield, enantio-, or ambidoselectivity.
- Chen, Fenglin,Zhang, Yao,Yu, Lei,Zhu, Shaolin
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supporting information
p. 2022 - 2025
(2017/02/15)
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- Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis
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Four new macrolactones, leptolyngbyolides A–D, were isolated from the cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar structures of leptolyngbyolides were determined by extensive NMR studies, although complete assignment of the abs
- Cui, Jin,Morita, Maho,Ohno, Osamu,Kimura, Tomoyuki,Teruya, Toshiaki,Watanabe, Takumi,Suenaga, Kiyotake,Shibasaki, Masakatsu
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supporting information
p. 8500 - 8509
(2017/06/28)
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- Catalytic asymmetric synthesis of key intermediate for scytophycin C
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We achieved a formal total synthesis of scytophycin C. The synthesis demonstrates the utility of the catalytic asymmetric direct thioamide-aldol reaction for the preparation of polyketide structures, and was accomplished via diastereoselective allylation,
- Cui, Jin,Watanabe, Takumi,Shibasaki, Masakatsu
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supporting information
p. 446 - 448
(2016/01/12)
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- Synthesis and reactivity of 1,2-dioxolanes from β,γ-epoxy ketones
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Five-membered ring peroxides were prepared in one step in 31-86% yield from readily accessible β,γ-epoxy ketones and H2O2. The reaction proceeded via a tetrahydrofuran, which was converted to the thermodynamically favored 1,2-dioxola
- Kandur, Wynne V.,Richert, Kathleen J.,Rieder, Curtis J.,Thomas, Andrew M.,Hu, Chunhua,Ziller, Joseph W.,Woerpel
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supporting information
p. 2650 - 2653
(2014/06/09)
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- Stereoselective synthesis of the C10-C18 fragment of iriomoteolide-3a
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An efficient synthesis of the highly stereogenic centered C10-C18 fragment of iriomoteolide-3a has been accomplished. Key steps include Sharpless asymmetric dihydroxylation and epoxidation for generation of the desired stereocenters. Georg Thieme Verlag Stuttgart · New York.
- Reddy, Chada Raji,Dharmapuri, Gajula
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p. 673 - 677
(2013/04/10)
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- Synthesis and biological activity of 7,8,9-trideoxy- and 7R DesTHP-peloruside A
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The stereoselective syntheses of 7,8,9-trideoxypeloruside A (4) and a monocyclic peloruside A analogue lacking the entire tetrahydropyran moiety (3) are described. The syntheses proceeded through the PMB-ether of an ω-hydroxy β-keto aldehyde as a common intermediate which was elaborated into a pair of diastereomeric 1,3-syn and -anti diols by stereoselective Duthaler-Hafner allylations and subsequent 1,3-syn or anti reduction. One of these isomers was further converted into a tetrahydropyran derivative in a high-yielding Prins reaction, to provide the precursor for bicyclic analogue 4. Downstream steps for both syntheses included the substrate-controlled addition of a vinyl lithium intermediate to an aldehyde, thus connecting the peloruside side chain to C15 (C13) of the macrocyclic core structure in a fully stereoselective fashion. In the case of monocyclic 3 macrocyclization was based on ring-closing olefin metathesis (RCM), while bicyclic 4 was cyclized through Yamaguchi-type macrolactonization. The macrolactonization step was surprisingly difficult and was accompanied by extensive cyclic dimer formation. Peloruside A analogues 3 and 4 inhibited the proliferation of human cancer cell lines in vitro with micromolar and sub-micromolar IC50 values, respectively. The higher potency of 4 highlights the importance of the bicyclic core structure of peloruside A for nM biological activity. I need the THP ring: Convergent stereoselective syntheses of mono- and bicyclic analogues 2 and 3 of the natural product mitosis inhibitor peloruside A (1) have been developed based on macrocyclization by ring-closing metathesis (2) or macrolactonization (3). Both analogues are less potent than natural 1, but the activity difference is distinctly less pronounced for bicyclic analogue 3. The bicyclic core structure of peloruside A thus appears to be a necessary, but not sufficient provision for peloruside A-like activity (IC50 = 2: 1-5 μM, 3: 100-300 nM). Copyright
- Wullschleger, Christoph W.,Gertsch, Jürg,Altmann, Karl-Heinz
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supporting information
p. 13105 - 13111
(2013/10/01)
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- Enantioselective synthesis of the C5-C23 segment of biselyngbyaside
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Stereo and enantioselective synthesis of C5-C23 fragment of cytotoxic marine natural product biselyngbyaside is achieved using E-selective methyl lithium addition onto enyne, Crimmin's acetate aldol reaction, Sharpless asymmetric epoxidation, and Julia-Kocienski olefination as the key steps.
- Chandrasekhar, Srivari,Rajesh, Gontla,Naresh, Tumma
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p. 252 - 255
(2013/02/23)
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- Fluorinated Pseudopeptide Analogues of the Neuropeptide 26RFa: Synthesis, Biological, and Structural Studies
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A series of four fluorinated dipeptide analogues each containing a fluoro-olefin moiety as peptide bond surrogate has been designed and synthesized. These motifs have been successfully introduced into the bioactive C-terminal heptapeptide of the neuropeptide 26RFa by conventional SPPS. We then evaluated the ability of the generated pseudopeptides to increase [Ca2+]i in GPR103-transfected cells. For these fluorinated analogues, greater stability in human serum was observed. Their conformations were also investigated, leading to the valuable identification of differences depending on the position of the fluoro-olefin moiety in the sequence.
- Pierry, Camille,Couve-Bonnaire, Samuel,Guilhaudis, Laure,Neveu, Cindy,Marotte, Amelie,Lefranc, Benjamin,Cahard, Dominique,Segalas-Milazzo, Isabelle,Leprince, Jerome,Pannecoucke, Xavier
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p. 1620 - 1633
(2013/09/23)
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- Stereocontrol in palladium-catalyzed propargylic substitutions: Kinetic resolution to give enantioenriched 1,5-enynes and propargyl acetates
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Kinetic resolution during the catalytic allyl-propargyl cross-coupling with chiral starting materials can be accomplished with a chiral palladium catalyst. These reactions offer ready access to enantiomerically enriched enyne products from simple, readily
- Ardolino, Michael J.,Eno, Meredith S.,Morken, James P.
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supporting information
p. 3413 - 3419
(2013/12/04)
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- Stereoselective synthesis of the C13-C28 subunit of (-)-laulimalide utilizing an α-chlorosulfide intermediate
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A stereoselective route to the C13-C28 subunit of (-)-laulimalide is described. l-Tartaric acid is the source of the hydroxy groups at C19 and C20. An α-chlorosulfide is employed as the key intermediate for the creation of the C17-C18 bond and the C16-C17 double bond was introduced using the Mislow-Braverman rearrangement and Hutchin's dexoxygenation with concomitant double bond transposition reaction. The C15 and C23 stereogenic centers were created using catalytic asymmetric reactions. The trisubstituted and trans-disubstituted alkenes were created stereoselectively by taking advantage of ring-closing metathesis and the Julia-Kocienski olefination reaction, respectively. Georg Thieme Verlag Stuttgart, New York.
- Raghavan, Sadagopan,Samanta, Pradip Kumar
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supporting information
p. 1983 - 1987
(2013/09/24)
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- HERBICIDAL ISOXAZOLO[5,4-B]PYRIDINES
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The invention relates to isoxazolo[5,4-b]pyridine compounds of formula (I), to the agriculturally useful salts of isoxazolo[5,4-b]pyridine compounds of formula (I), and to their use as herbicides.
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Page/Page column 56
(2013/07/25)
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- Total synthesis of (-)-zampanolide and structure-activity relationship studies on (-)-dactylolide derivatives
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A new total synthesis of the marine macrolide (-)-zampanolide (1) and the structurally and stereochemically related non-natural levorotatory enantiomer of (+)-dactylolide (2), that is, ent-2, has been developed. The synthesis features a high-yielding, selective intramolecular Horner-Wadsworth-Emmons (HWE) reaction to close the 20-membered macrolactone ring of 1 and ent-2. The β-keto phosphonate/aldehyde precursor for the ring-closure reaction was obtained by esterification of a ω-diethylphosphono carboxylic acid fragment and a secondary alcohol fragment incorporating the THP ring that is embedded in the macrocyclic core structure of 1 and ent-2. THP ring formation was accomplished through a segment coupling Prins-type cyclization. Employing the same overall strategy, 13-desmethylene-ent-2 as well as the monocyclic desTHP derivatives of 1 and ent-2 were prepared. Synthetic 1 inhibited human cancer cell growth in vitro with nM IC50 values, while ent-2, which lacks the diene-containing hemiaminal-linked side chain of 1, is 25- to 260-fold less active. 13-Desmethylene-ent-2 as well as the reduced versions of ent-2 and 13-desmethylene-ent-2 all showed similar cellular activity as ent-2 itself. The same activity level was attained by the monocyclic desTHP derivative of 1. Oxidation of the aldehyde functionality of ent-2 gave a carboxylic acid that was converted into the corresponding N-hexyl amide. The latter showed only μM antiproliferative activity, thus being several hundred-fold less potent than 1. It's the side chain that matters: The marine macrolide (-)-zampanolide (1) has been synthesized via (-)-dactylolide (ent-2), the non-natural enantiomer of the marine natural product (+)-dactylolide (2), employing a high-yielding intramolecular Horner-Wadsworth-Emmons reaction to close the macrolactone ring. While the hemiaminal-linked side chain in 1 is crucial for nanomolar antiproliferative activity, the methylene group and the aldehyde functionality in ent-2 are dispensable. A monocyclic destetrahydropyran derivative of 1 shows equal activity as ent-2. Copyright
- Zurwerra, Didier,Glaus, Florian,Betschart, Leo,Schuster, Julia,Gertsch, Jürg,Ganci, Walter,Altmann, Karl-Heinz
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supporting information
p. 16868 - 16883
(2013/03/14)
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- PRODRUGS OF GUANFACINE
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Prodrugs of guanfacine, pharmaceutical compositions containing such prodrugs and a method for providing therapeutic benefit in the treatment of ADHD/ODD (attention deficient hyperactivity disorder and oppositional defiance disorder) with guanfacine prodrugs are provided herein. Additionally, methods for improving the pharmacokinetics of guanfacine or minimizing or avoiding the adverse gastrointestinal side effects associated with guanfacine administration are provided herein.
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Page/Page column 18
(2012/03/27)
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- Total synthesis of the marine toxin phorboxazole A using palladium(ii)-mediated intramolecular alkoxycarbonylation for tetrahydropyran synthesis
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The potent antitumor agent phorboxazole A was synthesized from six subunits comprising C1-C2 (115), C3-C8 (98), C9-C19 (74), C20-C32 (52), C33-C41 (84) and C42-C46 (85). Tetrahydropyrans B and C containing cis-2,6-disubstitution were fabricated via palladium(ii)-mediated intramolecular alkoxycarbonylation which, in the case of tetrahydropyran C, was carried out with catalytic palladium(ii) and p-benzoquinone as the stoichiometric re-oxidant. Tetrahydropyran D was obtained by a stereoselective tin(iv)-catalyzed coupling of a C9 aldehyde with an allylsilane, and the C19-C20 connection was made using a completely stereoselective Wittig-Schlosser (E) olefination. Coupling of the oxazole C32 methyl substituent with the intact C33-C46 δ-lactone 3 was accompanied by elimination of the vinyl bromide to a terminal alkyne, but the C32-C33 linkage was implemented successfully with 83 and C33-C41 lactone 84. The C42-C46 segment of the side chain was then appended via Julia-Kocienski olefination. The macrolide portion of phorboxazole A was completed by means of an Ando-Still-Gennari intramolecular (Z)-selective olefination at C2-C3 which required placement of a (dimethoxyphosphinyl)acetate moiety at C24. Final deprotection led to phorboxazole A via a route in which the longest linear sequence is 37 steps and the overall yield is 0.36%.
- Kuntiyong, Punlop,Lee, Tae Hee,Kranemann, Christian L.,White, James D.
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supporting information
p. 7884 - 7899
(2013/07/05)
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- New anti-HIV aptamers based on tetra-end-linked DNA G-quadruplexes: Effect of the base sequence on anti-HIV activity
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This communication reports on the synthesis and biophysical, biological and SAR studies of a small library of new anti-HIV aptamers based on the tetra-end-linked G-quadruplex structure. The new aptamers showed EC50 values against HIV-1 in the r
- D'Atri, Valentina,Oliviero, Giorgia,Amato, Jussara,Borbone, Nicola,D'Errico, Stefano,Mayol, Luciano,Piccialli, Vincenzo,Haider, Shozeb,Hoorelbeke, Bart,Balzarini, Jan,Piccialli, Gennaro
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supporting information
p. 9516 - 9518
(2012/10/29)
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- Construction of 1,5-enynes by stereospecific Pd-catalyzed allyl-propargyl cross-couplings
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The palladium-catalyzed cross-coupling of chiral propargyl acetates and allyl boronates delivers chiral 1,5-enynes with excellent levels of chirality transfer and can be applied across a broad range of substrates.
- Ardolino, Michael J.,Morken, James P.
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supporting information; scheme or table
p. 8770 - 8773
(2012/07/02)
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- Molecular design, synthesis, and evaluation of novel potent apoptosis inhibitors inspired from bongkrekic acid
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Bongkrekic acid (BKA) is an inhibitor of adenine nucleotide translocase (ANT). Since inhibition of ANT is connected to the inhibition of cytochrome c release from mitochondria, which then results in the suppression of apoptosis, it has been used as a tool for the mechanistic investigation of apoptosis. BKA consists of a long carbon chain with two asymmetric centers, a nonconjugated olefin, two conjugated dienes, three methyl groups, a methoxyl group, and three carboxylic acids. This complicated chemical structure has caused difficulties in synthesis, supply, and biochemical mechanistic investigations. In this study, we designed and synthesized more simple tricarboxylic acids that were inspired by the molecular structure of BKA. Their cytotoxicity and apoptosis-preventing activity in HeLa cells and the effect on the mitochondrial inner membrane potential (Δψm) in HL-60 cells were then evaluated. All tested tricarboxylic acid derivatives including BKA showed little toxicity against HeLa cells. BKA and two of the synthesized derivatives significantly suppressed staurosporine (STS)-induced reductions in cell viability. Furthermore, STS-induced Δψm collapse was significantly restored by pretreatment with BKA and a tricarboxylic acid derivative. Other derivatives, in which one of three carboxylic acids was esterified, exhibited potent toxicity, especially a derivative bearing a carbon chain of the same length as that of BKA. In conclusion, we have developed a new lead compound as an apoptosis inhibitor bearing three carboxylic acids connected with the proper length of a long carbon chain.
- Okuda, Katsuhiro,Hasui, Keisuke,Abe, Masato,Matsumoto, Kenji,Shindo, Mitsuru
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p. 2253 - 2260
(2013/01/15)
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- Synthesis of fluorinated pseudopeptides: Metal mediated reversal of stereochemistry in diastereoselective addition of organometallic reagents to N-(tert-butanesulfinyl)-α-fluoroenimines
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The addition reaction of organometallic reagents to N-(tert-butanesulfinyl) -α-fluoroenimines was studied. Depending of the nature of the organometallic species (Grignard reagents or zincate complexes), we were able to control the configuration of the new
- Pierry, Camille,Cahard, Dominique,Couve-Bonnaire, Samuel,Pannecoucke, Xavier
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experimental part
p. 2378 - 2386
(2011/05/14)
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- Stereoselective synthesis (+)-cephalosporolide D
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A simple and efficient stereoselective synthesis of macrolactone, (+)-cephalosporolide D has been accomplished in 13 steps from inexpensive and commercially available starting materials in an overall yield of 17%, respectively. This convergent synthesis u
- Reddy, G. Venkateswar,Kumar, R. Sateesh Chandra,Sreedhar, Eppakayala,Babu, K. Suresh,Rao, J. Madhusudana
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scheme or table
p. 1723 - 1726
(2010/05/03)
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- Synthesis of the FG ring fragment of pectenotoxins 1-9
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The synthesis of the FG ring fragment common to pectenotoxins 1-9 is reported.The successful, convergent synthesis relied on high yielding routes to access two key intermediates; aldehyde 1 and phosphonium salt 2.A Z-selective Wittig reaction gave access
- Heapy, Amanda M.,Brimble, Margaret A.
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scheme or table
p. 5424 - 5431
(2010/08/13)
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- Probing a biomimetic approach to mycaperoxide B: Hydroperoxidation studies
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Hydroperoxidation studies on a series of alkene substrates demonstrate the introduction of the hydroperoxide functional group into the required position for a biosynthetically inspired synthesis of mycaperoxide B. Georg Thieme Verlag Stuttgart.
- Silva, Eduarda M.P.,Pye, Richard J.,Cardin, Christine,Harwood, Laurence M.
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scheme or table
p. 509 - 513
(2010/09/18)
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- Synthesis of disubstituted 1,2-dioxolanes, 1,2-dioxanes, and 1,2-dioxepanes
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A route to cyclic peroxides containing 1,2-dioxolane, 1,2-dioxane or 1,2-dioxepane rings is described. These compounds present simpler structures related to the bicyclic core of stolonoxides, metabolites with marked cytotoxicity against several mammalian
- Guerra, Francisco M.,Zubía, Eva,Ortega, María J.,Moreno-Dorado, F. Javier,Massanet, Guillermo M.
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scheme or table
p. 157 - 163
(2010/03/01)
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- First stereoselective total synthesis of decarestrictine O via RCM protocol
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A convergent first stereoselective total synthesis of decarestrictine O via RCM protocol starting from 1,3-propanediol and propylene oxide is reported.
- Krishna, Palakodety Radha,Rao, T. Jagannadha
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scheme or table
p. 4017 - 4019
(2010/08/07)
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- A convergent approach toward phoslactomycins and leustroducsins
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Synthetic studies devoted to the development of a convergent approach toward phoslactomycins and leustroducsins, a family of natural products inhibitors of serine/threonine phosphatase 2A, are reported. A formal synthesis of phoslactomycin B was achieved
- Druais, Valérie,Hall, Michael J.,Corsi, Camilla,Wendeborn, Sebastian V.,Meyer, Christophe,Cossy, Janine
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scheme or table
p. 6358 - 6375
(2010/10/19)
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- A convergent approach toward the C1-C11 subunit of phoslactomycins and formal synthesis of phoslactomycin b
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The preparation of the C1-C11 subunit of phoslactomycins, and a formal synthesis of phoslactomycin B, were achieved by a convergent strategy involving the chelation-controlled addition of an alkynyl Grignard reagent to an α-alkoxy ketone. Catalytic enanti
- Ais, Valerie Dru,Hall, Michael J.,Corsi, Camilla,Wendeborn, Sebastian V.,Meyer, Christophe,Cossy, Janine
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supporting information; experimental part
p. 935 - 938
(2009/08/07)
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- Synthetic study of fomitellic acids: construction of the AB ring moiety
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Stereocontrolled synthesis of a fully functionalized AB ring moiety of fomitellic acids was accomplished. The tricyclic skeleton was stereoselectively constructed by means of titanium(III)-mediated radical cascade cyclization of epoxypolyene. The stereoch
- Yamaoka, Makoto,Fukatsu, Yuichi,Nakazaki, Atsuo,Kobayashi, Susumu
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supporting information; experimental part
p. 3849 - 3852
(2009/10/11)
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- Chemoselective TBS deprotection of primary alcohols by means of pyridinium tribromide (Py·Br3) in MeOH
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A catalytic amount of pyridinium tribromide (Py·Br3) in MeOH chemoselectively deprotects primary TBS ethers in the presence of a variety of other protecting and common functional groups in modest to excellent yields when performed at 0 °C.
- Martinez-Solorio, Dionicio,Jennings, Michael P.
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p. 5175 - 5178
(2008/12/20)
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- Synthesis and evaluation of xanomeline analogs-Probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor
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A series of xanomeline analogs were synthesized and evaluated for binding at the M1 muscarinic acetylcholine receptor (M1 receptor). Specifically, compounds that substitute the O-hexyl chain of xanomeline with polar, ionizable, or conformationally restricted moieties were assessed for their ability to bind to the M1 receptor in a wash-resistant manner (persistent binding). From our screen, several novel ligands that persistently bind to the M1 receptor with greater affinity than xanomeline were discovered. Results indicate that persistent binding may arise not only from hydrophobic interactions but also from ionic interactions with a secondary M1 receptor binding site. Herein, a qualitative model that accounts for both binding scenarios is proposed and applied to understand the structural basis to wash-resistant binding and long-acting effects of xanomeline-based compounds.
- Kane, Brian E.,Grant, Marianne K.O.,El-Fakahany, Esam E.,Ferguson, David M.
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p. 1376 - 1392
(2008/09/18)
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- Total synthesis of (-)-basiliskamide B
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The total synthesis of the polyketide antibiotic (-)-basiliskamide B is described. The convergent asymmetric synthesis relies on the use of a diastereoselective ethyl ketone aldol reaction followed by a syn selective reduction of a β-hydroxy ketone and a
- Dias, Luiz C.,Goncalves, Caroline Da Costa S.
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body text
p. 1017 - 1021
(2009/05/27)
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- Cyclopentanone derivatives, method of synthesis and uses thereof
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The present invention relates to cyclopentanone derivatives of formula (I), their method of synthesis and uses thereof. Concretely, the compounds disclosed have proved to be inhibitors of glycogen synthase kinase 3β, GSK-3 β, which is known to be involved in different disease and conditions, such as Alzheimer's disease or non-insulin dependent diabetes mellitus. The present invention also relates to pharmaceutical compositions comprising the same. Further, the present invention is directed to the use of the compounds in the manufacture of a medicament for the treatment and/or prevention of a GSK-3 mediated disease or condition.
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Page/Page column 19-20
(2008/12/06)
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- Synthetic efforts toward the macrolactone core of leucascandrolide A
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(Chemical Equation Presented) A chemoselective synthesis of 1, the macrocyclic core of leucascandrolide A, has been achieved by utilizing highly enantioselective allylmetalations, an enantioselective Noyori reduction of a propargylic ketone, and olefin metatheses as the key steps.
- Ferrie, Laurent,Boulard, Lucie,Pradaux, Fabienne,Bouzbouz, Samir,Reymond, Sebastien,Capdevielle, Patrice,Cossy, Janine
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p. 1864 - 1880
(2008/09/18)
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- A new construction of 2-alkoxypyrans by an acylation-reductive cyclization sequence
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A new convergent synthetic approach to a pyran motif common to many naturally occurring structures is described. In this approach, two fragments are joined by esterification, and a subsequent intramolecular reductive cyclization affords the 2-hydroxypyran.
- Heumann, Lars V.,Keck, Gary E.
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p. 1951 - 1954
(2008/02/02)
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- A catalytic asymmetric vinylogous mukaiyama aldol reaction
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A vinylogous Mukaiyama aldol reaction, conducted using 10 mol % of a BITIP catalyst and B(OMe)3 as an additive, effects an enantioselective four-carbon chain extension to give versatile Eαβ-unsaturated thiol esters.
- Heumann, Lars V.,Keck, Gary E.
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p. 4275 - 4278
(2008/02/13)
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- SYNTHESIS OF CHLORINS AND PHORBINES WITH ENHANCED RED SPECTRAL FEATURES
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The present invention provides compounds of the general Formula DI: along with methods of making such compounds, formulations containing the same, and methods of using the same (e.g., in photodynamic therapy, for the production of solar cells, etc.).
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Page/Page column 124-125; 135
(2008/06/13)
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