472-20-8Relevant articles and documents
Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin
Bassetto, Marcella,Brancale, Andrea,Pasqualetto, Gaia,Pileggi, Elisa,Rozanowska, Malgorzata,Schepelmann, Martin,Varricchio, Carmine
supporting information, (2021/09/24)
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.
Highly pH-Dependent Chemoselective Transfer Hydrogenation of α,β-Unsaturated Aldehydes in Water
Luo, Nianhua,Liao, Jianhua,Ouyang, Lu,Wen, Huiling,Liu, Jitian,Tang, Weiping,Luo, Renshi
, p. 3025 - 3031 (2019/08/30)
The pH-dependent selective Ir-catalyzed hydrogenation of α,β-unsaturated aldehydes was realized in water. Using HCOOH as the hydride donor at low pH, the unsaturated alcohol products were obtained exclusively, while the saturated alcohol products were formed preferentially by employing HCOONa as the hydride donor at high pH. A wide range of functional groups including electron-rich as well as electron-poor substituents on the aryl group of α,β-unsaturated aldehydes can be tolerated, affording the corresponding products in excellent yields with high TOF values. High selectivity and yields were also observed for α,β-unsaturated aldehydes with aliphatic substituents. Our mechanistic investigations indicate that the pH value is critical to the chemoselectivity.
A general strategy for the stereoselective synthesis of the furanosesquiterpenes structurally related to pallescensins 1-2
Serra, Stefano
, (2019/05/24)
Here, we describe a general stereoselective synthesis of the marine furanosesquiterpenes structurally related to pallescensins 1-2. The stereoisomeric forms of the pallescensin 1, pallescensin 2, and dihydropallescensin 2 were obtained in high chemical and isomeric purity, whereas isomicrocionin-3 was synthesized for the first time. The sesquiterpene framework was built up by means of the coupling of the C10 cyclogeranyl moiety with the C5 3-(methylene)furan moiety. The key steps of our synthetic procedure are the stereoselective synthesis of four cyclogeraniol isomers, their conversion into the corresponding cyclogeranylsulfonylbenzene derivatives, their alkylation with 3-(chloromethyl)furan, and the final reductive cleavage of the phenylsulfonyl functional group to afford the whole sesquiterpene framework. The enantioselective synthesis of the α-, 3,4-dehydro-γ- and γ-cyclogeraniol isomers was performed using both a lipase-mediated resolution procedure and different regioselective chemical transformations.
