- Insights into Thiourea-Based Bifunctional Catalysts for Efficient Conversion of CO2to Cyclic Carbonates
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The bifunctional thiourea catalyst system with both electrophilic and nucleophilic centers has been certified to be effective for fixing CO2 under mild reaction conditions; however, many questions remain, especially concerning the relationship between str
- Li, Zhuo-Qun,Zhang, Yao-Yao,Zheng, Yu-Jia,Li, Bo,Wu, Guang-Peng
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p. 3145 - 3155
(2022/02/14)
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- Batch Versus Flow Lithiation–Substitution of 1,3,4-Oxadiazoles: Exploitation of Unstable Intermediates Using Flow Chemistry
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1,3,4-Oxadiazoles are a common motif in pharmaceutical chemistry, but few convenient methods for their modification exist. A fast, convenient, high yielding and general α-substitution of 1,3,4-oxadiazoles has been developed using a metalation-electrophilic trapping protocol both in batch and under continuous flow conditions in contradiction to previous reports which suggest that α-metalation of this ring system results in ring fragmentation. In batch, lithiation is accomplished at an industrially convenient temperature, ?30 °C, with subsequent trapping giving isolated yields of up to 91 %. Under continuous flow conditions, metalation is carried out at room temperature, and subsequent in flow electrophilic trapping gave up to quantitative isolated yields. Notably, lithiation in batch at room temperature results only in ring fragmentation and we propose that the superior mixing in flow allows interception and exploitation of an unstable intermediate before decomposition can occur.
- Wong, Jeff Y. F.,Tobin, John M.,Vilela, Filipe,Barker, Graeme
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supporting information
p. 12439 - 12445
(2019/09/06)
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- Regioselective covalent modification of hemoglobin in search of antisickling agents
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Although the molecular defect in sickle hemoglobin that produces sickle cell disease has been known for decades, there is still no effective drug treatment that acts on hemoglobin itself. In this work, a series of diversely substituted isothiocyanates (R-NCS) were examined for their regioselective reaction with hemoglobin in an attempt to alter the solubility properties of sickle hemoglobin. Electrospray mass spectrometry, molecular modeling, X-ray crystallography, and conventional protein chemistry were used to study this regioselectivity and the resulting increase in solubility of the modified hemoglobin. Depending on the attached R-group, the isothiocyanates were found to react either with the Cysβ93 or the N-terminal amine of the α-chain. One of the most effective compounds in the series, 2-(N,N-dimethylamino)ethyl isothiocyanate, selectively reacts with the thiol of Cysβ93 which, in conjunction with the cationic group, was seen to perturb the local hemoglobin structure. This modified HbS shows an approximately 30% increase in solubility for the fully deoxygenated state, along with a significant increase in oxygen affinity. This compound and a related analogue appear to readily traverse the erythrocyte membrane. A discussion of the relation of these structural changes to inhibition of gelation is presented. The dual activities of increasing HbS oxygen affinity and directly inhibiting deoxy HbS polymerization, in conjunction with facile membrane traversal, suggest that these cationic isothiocyanates show substantial promise as lead compounds for development of therapeutic agents for sickle cell disease.
- Park, Soobong,Hayes, Brittany L.,Marankan, Fatima,Mulhearn, Debbie C.,Wanna, Linda,Mesecar, Andrew D.,Santarsiero, Bernard D.,Johnson, Michael E.,Venton, Duane L.
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p. 936 - 953
(2007/10/03)
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- Synthesis and screening of conformationally restricted and conformationally free N-(tertiary aminoalkyl)dithiocarbamic acids and esters as inhibitors of neuronal nitric oxide synthase
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N-(Tertiary aminoalkyl)dithiocarbamic acids and esters were synthesized and evaluated for their ability to inhibit neuronal nitric oxide synthase. Preliminary results show these compounds are able to act at the binding site for l-arginine and the conformationally restricted esters may have a second site of activity involving the cofactor (6R)-5,6,7,8-tetrahydro-l-biopterin. Copyright (C) 1997 Elsevier Science Ltd.
- Sassaman, Mark B.,Giovanelli, John,Sood, Virendar K.,Eckelman, William C.
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p. 1759 - 1766
(2007/10/03)
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- Anthelmintic 1-(substituted phenyl)-3-alkanimidoyl ureas
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The compounds of this invention are novel imidoylureas having anthelmintic activity and imidoylthioureas having antifertility activity. They are prepared by the reaction of appropriate amidines with appropriate isocyanates or isothiocyanates.
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