875-72-9Relevant academic research and scientific papers
Synthesis of Adamantane Derivatives. 50. Facile Synthesis of 2,4-Oxa-Bridged Protoadamantanes and Their Conversions to 2-Substituted and 2,4-Disubstituted Protoadamantanes and a 2,4-Disubstituted Adamantane
Sasaki, Tadashi,Eguchi, Shoji,Suzuki, Takanori
, p. 3824 - 3827 (1980)
Intramolecular Paterno-Buechi reaction of 3-endo-acylbicyclonon-6-enes 1a,b proceeded regioselectively to afford exclusively 2,4-oxa-bridged protoadamantanes 2a,b in good yields.The oxetane rings of 2a and 2b were cleaved by addition of hydrogen halides and by reduction with LiAlH4, affording stereospecifically the corresponding 2,4-disubstituted and 2-substituted protoadamantane derivatives 7a, 7b, 9, and 10, respectively.Dehydration of 2-exo-methyl-2-endo-hydroxyprotoadamantane (10) with POCl3-pyridine gave 2-methyleneprotoadamantane (11), while dehydration of the corresponding 4-exo-chloro derivative (7b) afforded exclusively 4(e)-chloro-2-methyleneadamantane (14) as a rearranged product in a high yield.
Synthetic Photochemistry. LX. One-pot Formation of Spirocyclic 3-Acetyl-2-hydroxy-2-cyclopentenone Derivatives from Methylenecycloalkanes and Methyl 2,4-Dioxopentanoate
Hatsui, Toshihide,Ikeda, Shin-ya,Takeshita, Hitoshi
, p. 870 - 876 (1993)
A series of proto-photocycloadducts of methyl 2,4-dioxopentanoate to methylenecycloalkanes and -alkenes spontaneously caused retro-benzilic acid rearrangement in high yields.The results are utterly different from those of sterically-crowded acyclic alkenes, with which the rearrangement occurred by thermolysis as a minor process.
A Novel Tumor-Activated Prodrug Strategy Targeting Ferrous Iron Is Effective in Multiple Preclinical Cancer Models
Spangler, Benjamin,Fontaine, Shaun D.,Shi, Yihui,Sambucetti, Lidia,Mattis, Aras N.,Hann, Byron,Wells, James A.,Renslo, Adam R.
, p. 11161 - 11170 (2016)
Here we describe a new approach for tumor targeting in which augmented concentrations of Fe(II) in cancer cells and/or the tumor microenvironment triggers drug release from an Fe(II)-reactive prodrug conjugate. The 1,2,4-trioxolane scaffold developed to enable this approach can in principle be applied to a broad range of cancer therapeutics and is illustrated here with Fe(II)-targeted forms of a microtubule toxin and a duocarmycin-class DNA-alkylating agent. We show that the intrinsic reactivity/toxicity of the duocarmycin analog is masked in the conjugated form and this greatly reduced toxicity in mice. This in turn permitted elevated dosing levels, leading to higher systemic exposure and a significantly improved response in tumor xenograft models. Overall our results suggest that Fe(II)-dependent drug delivery via trioxolane conjugates could have significant utility in expanding the therapeutic index of a range of clinical and preclinical stage cancer chemotherapeutics.
Energetics and Structure of the 1- and 2-Adamantyl Radicals and Their Corresponding Carbonium Ions by Photoelectron Spectroscopy
Kruppa, Gary H.,Beauchamp, J. L.
, p. 2162 - 2169 (1986)
The first photoelectron bands of the 1- and 2-adamantyl radicals, formed by flash vacuum photolysis of 1- and 2-adamantylmethyl nitrite, have been obtained.The adiabatic (IPa) and vertical (IPv) ionization potentials of the 1-adamantyl radical are 6.21 +/- 0.03 and 6.36 +/- 0.05 eV, respectively.IPa and IPv for the 2-adamantyl radical are 6.73 +/- 0.03 and 6.99 +/- 0.05 eV, respectively.The difference in hydride affinities between the 1-adamantyl and tert-butyl cations (Sharma, R.B.; Sen Sharma, D.K.; Hiraoka, K.; Kebarle, P.J.Am.Chem.Soc. 1985, 107, 3747) combined with the difference in IPa between the tert-butyl and 1-adamantyl radicals (0.49 +/- 0.06 eV) yield a value of 99 kcal/mol for the tertiary C-H bond energy in adamantane, 3.7 +/- 1.2 kcal/mol greater than the tertiary C-H bond energy in isobutane (assumed to be 95 kcal/mol).The effects of the geometrical constraints imposed by the adamantyl cage on the homolytic and heterolytic C-H-bond cleavage energies are disscussed for the 1- and 2-adamantyl cases.The width of the Franck-Condon envelope obtained is related to the geometry changes that occur upon ionization.The surprisingly broad envelope observed for the planar 2-adamantyl radical indicates that the Franck-Condon envelope for the 1-adamantyl radical should not be interpreted as exclusively due to changes at the bridgehead position.Thermal decomposition products of the 1- and 2-adamantyl radicals are observed, and the pathways for thermal decompositions of the radicals are discussed.To confirm expected trends in ionization potentials and band shapes or tertiary radicals, the first photoelectron band of the 2-methyl-2-butyl radical has been obtained.The IPa of the 2-methyl-2-butyl radical is 6.65 +/- 0.04 eV with IPv = 6.91 +/- 0.05 eV.
One-Pot Preparation of Crowded Olefins from Hindered Ketones with Alkyllithiums and Thionyl Chloride
Olah, George A.,Wu, An-hsiang,Farooq, Omar
, p. 1375 - 1378 (1989)
A series of crowded olefins were prepared in high yield by the one-pot reaction of in situ generated lithium alkoxides, formed from hindered ketones and alkyllithiums, with thionyl chloride.The prepared olefins are generally inaccessible by either the Wittig reaction or using Grignard reagents becouse of predominant electron transfer-reduction of hindered ketones.
Oxo 2-Adamantylidene Complexes of Mo(VI) and W(VI)
Boudjelel, Maxime,Zhai, Feng,Schrock, Richard R.,Hoveyda, Amir H.,Tsay, Charlene
supporting information, p. 838 - 842 (2021/04/09)
Molybdenum and tungsten oxo 2-adamantylidene (Adene) complexes that contain two nonafluoro-tert-butoxide (ORF9) ligands have been prepared through addition of 2-methylene-or 2-ethylideneadamantane to neophylidene or neopentylidene complexes. The isolated oxo complexes include W(O)(Adene)(ORF9)2(PPh2Me) (1W), W(O)(Adene)(ORF9)2 (2W), W(O)(Adene)(2,5-dimethylpyrrolide)2 (3W), W(O)(Adene)(2,5-dimethylpyrrolide)(2,6-dimesitylphenoxide) (4W), Mo(O)(Adene)(ORF9)2(PPhMe2) (1Mo), and Mo(O)(Adene)(ORF9)2 (2Mo). Compound 2W is a dimer that contains unsymmetrically bridging oxo ligands; it dissociates readily and reversibly into monomers, especially in the presence of a donor such as THF. In contrast, 2Mo is a monomer. Both 2W and 2Mo are remarkably stable thermally. The pale-blue complexes Mo(Adene)(ORF9)2Cl2 (5Mo) and W(Adene)(ORF9)2Cl2 (5W) are formed upon addition of PCl5 to 2Mo and 2W, respectively. The oxo complexes are reactive olefin metathesis initiators, while 5Mo and 5W are relatively poor initiators. We ascribe the thermal stability of 2Mo and 2W to resistance of the 2-adamantylidene ligands to couple bimolecularly, to the absence of an α-hydrogen in the alkylidene, or both.
Methylenation for Aldehydes and Ketones Using 1-Methylbenzimidazol-2-yl Methyl Sulfone
Ando, Kaori,Oguchi, Mai,Kobayashi, Takahisa,Asano, Haruka,Uchida, Nariaki
, p. 9936 - 9943 (2020/09/04)
The methylenation reagent 1-methylbenzimidazol-2-yl methyl sulfone 2 reacts with various aldehydes and ketones in the presence of t-BuOK (room temperature, 1 h) in dimethylformamide to give the corresponding terminal alkenes generally in high yields. For sensitive substrates, the reaction is better carried out at low temperature using sodium hexamethyldisilazide in 1,2-dimethoxyethane. The byproduct is easily removed from the products, and the reaction conditions are mild and practical. Reagent 2 can be easily prepared from commercially available 2-mercaptobenzimidazole 5 in 95% yield without any expensive reagents.
Synthesis of Functionalized α-Vinyl Aldehydes from Enaminones
Chen, Jie,Guo, Pan,Zhang, Jianguo,Rong, Jiaxin,Sun, Wangbin,Jiang, Yaojia,Loh, Teck-Peng
supporting information, p. 12674 - 12679 (2019/08/07)
An efficient RhII-catalyzed synthesis of functionalized α-vinyl aldehydes with high E/Z stereoselectivity was developed. The reaction mediates the cyclopropanation of enaminones with vinyl carbenoids that are generated from cyclopropenes in situ to give the aminocyclopropane intermediates. Selective C?C bond cleavage of the cyclopropane intermediates leads to formation of α-vinyl aldehyde derivatives with high E/Z selectivity. This method proceeds at room temperature under very mild reaction conditions and works with a broad substrate scope.
COMPOUNDS AND METHODS FOR IDO AND TDO MODULATION, AND INDICATIONS THEREFOR
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Paragraph 0401, (2019/10/15)
Disclosed are compounds of Formula (I) and (Ia) or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R4, R5, R6, and R7 are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.
COMPOUNDS AND METHODS FOR IDO AND TDO MODULATION, AND INDICATIONS THEREFOR
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Paragraph 0536, (2018/04/20)
Disclosed are compounds of Formula I (a) or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein R4, R5, R6, R7, G1, G2 and Ring A are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.
