- Asymmetric C–H activation as a modern strategy towards expedient synthesis of steganone
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A formal synthesis of (+)-steganone by means of atroposelective C–H activation is reported. The herein described strategy is very straightforward as the targeted scaffold is afforded in only 10 steps, amongst which five of them are conducted without isola
- Dherbassy, Quentin,Wencel-Delord, Joanna,Colobert, Fran?oise
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- Heteroatom-containing novel high B-ring berberine analogues and C-H activation synthesis method thereof
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The invention provides a heteroatom-containing novel high B-ring berberine analogue and a C-H activation synthesis method thereof. The novel high-B-ring berberine analogue with the potential p300 histone acetyltransferase inhibitory activity is prepared f
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Paragraph 0011; 0014-0015
(2020/11/02)
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- Fused Amino Pyridines for the Treatment of Lung Cancer
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The present invention relates to the use of compounds with fused amino pyridine core for the treatment of malignancies associated with brain and lung. The oral administration of compounds of the instant application results in effective brain penetration and provides for non-intrusive treatment of brain and lung tumors.
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Paragraph 0149
(2016/11/17)
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- Access to Atropisomerically En-riched Biaryls by the Coupling of Aryllithiums with Arynes under Control by Homochiral Oxazolines
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We report the preparation of axially stereoenriched biphenyls by the coupling of in situ generated aryllithiums and arynes using chiral oxazoline auxiliaries. The design of the aryne precursors, the choice of oxazoline and the reaction conditions were key to accessing the desired, highly substituted, atropisomerically enriched biarylic products. In one case, the two atropo-diastereomers could be obtained in isomerically pure form by column chromatographic separation and their absolute configurations established by X-ray crystallography. The stereoselectivity of the reaction seems to be governed by subtle parameters.
- Yalcouye, Boubacar,Berthelot-Bréhier, Ana?s,Augros, David,Panossian, Armen,Choppin, Sabine,Chessé, Matthieu,Colobert, Fran?oise,Leroux, Frédéric R.
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supporting information
p. 725 - 732
(2017/01/18)
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- Atropo-diastereoselective coupling of aryllithiums and arynes — variations around the chiral auxiliary
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The atropo-selective coupling of in situ generated arynes and aryllithiums bearing various chiral auxiliaries ortho to lithium (tert-butylsulfoxide, para-tolylsulfoxide, tartrate-derived chiral diethers and oxazolines) is described. Chiral oxazolines showed the best results in terms of yields of coupling products. Different reaction parameters like the nature of the aryne precursor, the oxazoline, the alkyllithium base or the solvent revealed to be crucial for obtaining good yields and for diastereoselection.
- Augros, David,Yalcouye, Boubacar,Berthelot-Bréhier, Ana?s,Chessé, Matthieu,Choppin, Sabine,Panossian, Armen,Leroux, Frédéric R.
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p. 5208 - 5220
(2016/08/02)
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- FUSED AMINO PYRIDINES FOR THE TREATMENT OF BRAIN TUMORS
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The present invention relates to the use of compounds with fused amino pyridine core for the treatment of malignancies associated with brain and lung. The oral administration of compounds of the instant application results in effective brain penetration and provides for non-intrusive treatment of brain and lung tumors.
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- HSP90 Inhibitors Containing a Zinc Binding Moiety
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The present invention relates to HSP90 inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
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Page/Page column 36
(2008/12/08)
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- FUSED AMINO PYRIDINE AS HSP90 INHIBITORS
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The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.
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Page/Page column 38
(2008/12/08)
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- PtCl2-catalyzed hydrative cyclization of trialkyne functionalities to form bicyclic spiro ketones
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(Chemical Equation Presented) Triple rounds: A regioselective hydrative cyclization of triynes has been developed to give bicyclic β-hydroxy spiro ketones, which undergo subsequent dehydration to give the β,γ- unsaturated ketones (see scheme). Model reactions suggest that this platinum catalysis includes two selective hydrations, an alkyne insertion, and an aldol condensation.
- Chang, Hsu-Kai,Datta, Swarup,Das, Arindam,Odedra, Arjan,Liu, Rai-Shung
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p. 4744 - 4747
(2008/02/08)
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- Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90
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Hsp90 is a chaperone protein that allows cancer cells to tolerate the many components of dysregulated pathways. Its inactivation may result in targeting multiple molecular alterations and, thus, in reverting the transformed phenotype. The PU-class, a purine-scaffold Hsp90 inhibitor series, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of this class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. The study identifies water soluble derivatives (> 5 mM in PBS pH 7.4) of nanomolar potency (IC50 ~ 50 nM) in cellular and animal models of cancer. Binding affinities of these compounds for Hsp90 correlate well with their biological activities. When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenografted tumors, these agents result in pharmacologically relevant concentrations and, accordingly, in modulation of Hsp90-client proteins in tumors.
- He, Huazhong,Zatorska, Danuta,Kim, Joungnam,Aguirre, Julia,Llauger, Laura,She, Yuhong,Wu, Nian,Immormino, Robert M.,Gewirth, Daniel T.,Chiosis, Gabriela
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p. 381 - 390
(2007/10/03)
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- Iodination of alkyl aryl ethers by mercury(II) oxide-iodine reagent in dichloromethane
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A convenient method for selective mono- and diiodination of alkyl aryl ethers by mercury(II) oxide-iodine reagent in dichloromethane is reported.
- Orito,Hatakeyama,Takeo,Suginome
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p. 1273 - 1277
(2007/10/02)
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- Efficient Syntheses of Vinyl Ethers of Spiroquinol Ketals and Their High-Yield Photochemical Oxygen-to-Carbon -Shift to Spiro-Fused 2,5-Cyclohexadienones
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An efficient route to spiroquinol vinyl ethers involves addition of a 1-lithio-2-(trimethylsilyl)acetylene-substituted benzene to the monoethyleneketal of benzoquinone followed by desilylation/cyclization of the resulting product to give vinyl ethers of spiroquinol ketals.A high-yield photochemical conversion of these vinyl ethers of spiroquinol ketals to ketals of spiro-fused 2,5-cyclohexadienones has been developed.A complication in some of these photochemical reactions is formation of secondary products from light absorbed by the product, spiro dienone ketals.This has been solved by conducting the reaction in the presence of piper ylene, which quenches the triplet-state chemistry of the product spiro dienone ketal without altering the singlet excited-state chemistry of the quinol ketal vinyl ether.The quantum yield for the photochemical -shift reaction in a methyl-substituted vinyl ether is 0.4.Finally, irradiation of quinol spiro vinyl ethers was also observed to give spiro dienones in good yields.Although the spiro dienone is absorbing light in competition with starting quinol vinyl ether in this system, a high yield of product was obtained.The unexpected photochemical stability of these spiro dienones is discussed.The chemistry reported herein establishes an efficient high-yield route to spiro-fused 2,5-cyclohexadienones and their ketals under very mild conditions.
- Swenton, John S.,Callinan, Andrew,Wang, Shaopeng
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- 1,5-EPOXY-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINS AND USE IN TREATMENT OF ULCERS
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The synthesis of epoxybenzazepin compounds is described. The novel compounds have anti-ulcer activity.
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- Stereoselective Synthesis of an Analogue of Podophyllotoxin by an Intramolecular Diels-Alder Reaction
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The dihydrobenzocyclobutene 90 having a 4-hydroxycrotonate unit attached via an ester linkage as an internal dienophile can be cyclized to a 3:1 mixture of the trans lactone 92 (an analogue of podophyllotoxin, 1) and the cis lactone 93.This stereoselective reaction proceeds via the intermediacy of the o-quinodimethane 91 which cyclizes from the endo transition state 91n in preference to the exo-one 91x, presumably because of stabilization of the former by secondary orbital overlap.This result provides evidence that a proposed general route to the synthesis of podophyllotoxin, 1, and its analogues via the internal cycloaddition of the o-quinodimethane 8 to 9n may prove successful.Several possible approaches to the synthesis of the trans-2-aryldihydrobenzocyclobutenol 4 are described.The benzyne 11 was prepared and underwent but no cycloadditions.Although the 2-bromobenzocyclobutenone 23 could be synthesized in an efficient manner, it proved impossible to convert it into 4 by means of the aryl organometallic reagents 22ab.The bromo epoxide 52 was prepared and subjected to metal-halogen exchange and Lewis acid catalyzed epoxide rearrangement in an attempt to prepare 4.The aldehyde 56 was obtained in this reaction, clearly indicating that the desired intermediate 54 had been formed but could not be trapped under these conditions.Two ring contraction routes to 4 are also described, both beginning with the 1-indanone 74 prepared in good yield from piperonal 14.The diol monomesylate 78, prepared from 74, suffered base-catalyzed E2 elimination rather than the desired rearrangement to 80.The diazo ketone 83 underwent Wolff rearrangement to give the desired ester 84, but only in 7percent yield.Two interesting transformations were observed in these ring contraction schemes, namely the formation of the oxathiole dioxide 77 on mesylation of the ketol 75 and the preparation of the diazirene 86 on photolysis of the diazo ketone 83 at long wavelengths.The ester 84 was then saponified to the acid 87 which was coupled with methyl 4-hydroxycrotonate, 5, to give 90.The assignment of the structures of the products of thermolysis of 90 was based on high field 1H NMR and analogy to the spectra of similar compounds in the literature.
- Jung, Michael E.,Lam, Patrick Yuk-Sun,Mansuri, Muzzamil M.,Speltz, Laurine M.
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p. 1087 - 1105
(2007/10/02)
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