- Enantiospecific Synthesis of ortho-Substituted Benzylic Boronic Esters by a 1,2-Metalate Rearrangement/1,3-Borotropic Shift Sequence
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Coupling reactions between benzylamines and boronic esters have been investigated. ortho-Lithiated benzylamines react with boronic esters and a N-activator to afford ortho-substituted benzylic boronic esters with formal 1,1′-benzylidene insertion into the C-B bond. The reaction occurs by a SN2′ elimination and 1,2-metalate rearrangement of the N-activated boronate complex to afford a dearomatized intermediate, which undergoes a Lewis-acid catalyzed 1,3-borotropic shift to afford the boronic ester products in high yield and with excellent enantiospecificity. The use of enantioenriched α-substituted benzylamines gave the corresponding secondary boronic esters with high ee.
- Aichhorn, Stefan,Bigler, Raphael,Myers, Eddie L.,Aggarwal, Varinder K.
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supporting information
p. 9519 - 9522
(2017/07/25)
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- A simple and efficient strategy to enhance the antioxidant activities of amino-substituted glutathione peroxidase mimics
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The glutathione peroxidase (GPx) activities of some diaryl diselenides incorporating tertiary amino groups were studied with H2O 2, Cum-OOH, and tBuOOH as substrates and with PhSH as thiol co-substrate. Simple replacement of a hydrogen atom with a methoxy group dramatically enhances the GPx activity. The introduction of methoxy substituents ortho to selenium in N,N-dialkylbenzylamine-based compounds makes the basicity of the amino groups perfect for the catalysis. The presence of 6-OMe groups prevents possible Se-N interactions in the selenols, increasing their zwitterionic characters. The methoxy substituents also protect the selenium in the selenenic acid intermediates from overoxidation to seleninic acids or irreversible inactivation to selenonic acid derivatives. The additional substituents also play a crucial role in the selenenyl sulfide intermediates, by preventing thiol exchange reactions-which would normally lead to an inactivation pathway-at the selenium centers. The strengths of Se...N interactions in the selenenyl sulfide intermediates are dra-matically reduced upon introduction of the methoxy substituents, which not only reduce the thiol exchange reactions at selenium but also enhance the nucleophilic attack of the incoming thiols at sulfur. The facile attack of thiols at sulfur in the selenenyl sulfides also prevents the reactions between the selenenyl sulfides and H2O2 that can regenerate the selenenic acids (reverseGPx cycle). These studies reveal that the simple 6-OMe groups play multiple roles in each of the catalytically active intermediates by introducing steric and electronic effects that are required for efficient catalysis.
- Bhabak, Krishna P.,Mugesh, Govindasamy
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supporting information; experimental part
p. 8640 - 8651
(2009/10/24)
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- Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3
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Fused tricyclic compounds, methods of using such compounds in the treatment of hormone sensitive diseases such as prostate cancer, and pharmaceutical compositions containing such compounds.
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Page/Page column 65
(2010/02/14)
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- Radioiodinated analogs of xylamine: N-(2-chloroethyl)-N-ethyl-2-[125I]iodobenzylamine and N,N-diethyl-2-[125I)iodo benzylamine as potential tools for monoamine uptake exploration by SPECT
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In order to improve the scintigraphy and radiotherapy of neuroendocrine tumors we synthesized two radioiodinated benzylamines [N-(2-chloroethyl)-N-ethyl-2-[125I]iodobenzylamine and N,N-diethyl-2-[125I]iodobenzylamine], analogs of xylamine [N-(2-chloroethyl)-N-ethyl-2-methylbenzylamine]. Xylamine is an irreversible inhibitor of uptake and accumulation of noradrenaline. The two unlabelled iodinated derivatives [N-(2-chloroethyl)-N-ethyl-2-iodobenzylamine and N,N-diethyl-2-iodobenzylamine] were synthesized, purified and checked by HPLC, NMR and mass spectrography. Their affinity for the noradrenaline transporter was determined in vitro on rat brain membrane homogenates with [3H]nisoxetine. Radioiodination was performed by iodide for bromide nucleophilic exchange from brominated precursors. The N,N-diethyl-2-[125I]iodobenzylamine was obtained directly from N,N-diethyl-2-bromobenzylamine. Radiosynthesis of N-(2-chloroethyl)-Nethyl-2-[125I]iodobenzylamine required three steps. A new brominated precursor [N-ethyl-N-(2-bromobenzyl)glycine ethyl ester] which was stable for radiolabelling and suitable for reduction to N-(2-hydroxyethyl)-N-ethyl-2-[125I]iodobenzylamine was synthesized. N-(2-Hydroxyethyl)-N-ethyl-2-[125I]iodobenzylamine was converted to N-(2-chloroethyl)-N-ethyl-2-[125I]iodobenzylamine in the presence of an excess of thionyl chloride. Radioiodinated derivatives were purified and checked by HPLC.
- Branger,Garreau,Frangin,Chalon,Dubois,Dognon,Ombetta-Goka,Besnard,Guilloteau
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p. 685 - 699
(2007/10/02)
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