105536-22-9Relevant articles and documents
Boron trichloride as an efficient and selective agent for deprotection of tert-butyl aryl sulfonamides
Wan, Yiqian,Wu, Xiongyu,Kannan, Mahalingam A.,Alterman, Mathias
, p. 4523 - 4525 (2003)
A fast, mild and selective method for deprotection of tert-butyl aryl sulfonamides utilizing BCl3 as deprotection reagent has been developed. A variety of tert-butyl aryl sulfonamides used under these conditions gave the corresponding primary sulfonamides in high yields. The method does not cleave methoxy groups and prevents incorporation of tert-butyl groups onto electron-rich aromatic rings.
C?H Amination via Nitrene Transfer Catalyzed by Mononuclear Non-Heme Iron-Dependent Enzymes
Vila, Maria Agustina,Steck, Viktoria,Rodriguez Giordano, Sonia,Carrera, Ignacio,Fasan, Rudi
, p. 1981 - 1987 (2020)
Expanding the reaction scope of natural metalloenzymes can provide new opportunities for biocatalysis. Mononuclear non-heme iron-dependent enzymes represent a large class of biological catalysts involved in the biosynthesis of natural products and catabolism of xenobiotics, among other processes. Here, we report that several members of this enzyme family, including Rieske dioxygenases as well as α-ketoglutarate-dependent dioxygenases and halogenases, are able to catalyze the intramolecular C?H amination of a sulfonyl azide substrate, thereby exhibiting a promiscuous nitrene transfer reactivity. One of these enzymes, naphthalene dioxygenase (NDO), was further engineered resulting in several active site variants that function as C?H aminases. Furthermore, this enzyme could be applied to execute this non-native transformation on a gram scale in a bioreactor, thus demonstrating its potential for synthetic applications. These studies highlight the functional versatility of non-heme iron-dependent enzymes and pave the way to their further investigation and development as promising biocatalysts for non-native metal-catalyzed transformations.
P450-Catalyzed intramolecular sp3 C-H Amination with arylsulfonyl azide substrates
Singh, Ritesh,Bordeaux, Melanie,Fasan, Rudi
, p. 546 - 552 (2014)
The direct amination of aliphatic C-H bonds represents a most valuable transformation in organic chemistry. While a number of transition-metal-based catalysts have been developed and investigated for this purpose, the possibility to execute this transformation with biological catalysts has remained largely unexplored. Here, we report that cytochrome P450 enzymes can serve as efficient catalysts for mediating intramolecular benzylic C-H amination reactions in a variety of arylsulfonyl azide compouds. Under optimized conditions, the P450 catalysts were found to support up to 390 total turnovers leading to the formation of the desired sultam products with excellent regioselectivity. In addition, the chiral environment provided by the enzyme active site allowed for the reaction to proceed in a stereo- and enantioselective manner. The C-H amination activity, substrate profile, and enantio/stereoselectivity of these catalysts could be modulated by utilizing enzyme variants with engineered active sites.
Mechanism-Guided Design and Discovery of Efficient Cytochrome P450-Derived C-H Amination Biocatalysts
Fasan, Rudi,Kolev, Joshua N.,Ren, Xinkun,Steck, Viktoria
, p. 10343 - 10357 (2020)
Cytochromes P450 have been recently identified as a promising class of biocatalysts for mediating C-H aminations via nitrene transfer, a valuable transformation for forging new C-N bonds. The catalytic efficiency of P450s in these non-native transformations is however significantly inferior to that exhibited by these enzymes in their native monooxygenase function. Using a mechanism-guided strategy, we report here the rational design of a series of P450BM3-based variants with dramatically enhanced C-H amination activity acquired through disruption of the native proton relay network and other highly conserved structural elements within this class of enzymes. This approach further guided the identification of XplA and BezE, two atypical natural P450s implicated in the degradation of a man-made explosive and in benzastatins biosynthesis, respectively, as very efficient C-H aminases. Both XplA and BezE could be engineered to further improve their C-H amination reactivity, which demonstrates their evolvability for abiological reactions. These engineered and natural P450 catalysts can promote the intramolecular C-H amination of arylsulfonyl azides with over 10 000-14 000 catalytic turnovers, ranking among the most efficient nitrene transfer biocatalysts reported to date. Mechanistic and structure-reactivity studies provide insights into the origin of the C-H amination reactivity enhancement and highlight the divergent structural requirements inherent to supporting C-H amination versus C-H monooxygenation reactivity within this class of enzymes. Overall, this work provides new promising scaffolds for the development of nitrene transferases and demonstrates the value of mechanism-driven rational design as a strategy for improving the catalytic efficiency of metalloenzymes in the context of abiological transformations.
Novel fatty acid binding protein 4 (FABP4) inhibitors: Virtual screening, synthesis and crystal structure determination
Cai, Haiyan,Liu, Qiufeng,Gao, Dingding,Wang, Ting,Chen, Tiantian,Yan, Guirui,Chen, Kaixian,Xu, Yechun,Wang, Heyao,Li, Yingxia,Zhu, Weiliang
, p. 241 - 250 (2015)
Fatty acid binding protein 4 (FABP4) is a potential drug target for diabetes and atherosclerosis. For discovering new chemical entities as FABP4 inhibitors, structure-based virtual screening (VS) was performed, bioassay demonstrated that 16 of 251 tested compounds are FABP4 inhibitors, among which compound m1 are more active than endogenous ligand linoleic acid (LA). Based on the structure of m1, new derivatives were designed and prepared, leading to the discovery of two more potent inhibitors, compounds 9 and 10. To further explore the binding mechanisms of these new inhibitors, we determined the X-ray structures of the complexes of FABP4-9 and FABP4-10, which revealed similar binding conformations of the two compounds. Residue Ser53 and Arg126 formed direct hydrogen bonding with the ligands. We also found that 10 could significantly reduce the levels of lipolysis on mouse 3T3-L1 adipocytes. Taken together, in silico, in vitro and crystallographic data provide useful hints for future development of novel inhibitors against FABP4.
Chemoselective, enzymatic C-H bond amination catalyzed by a cytochrome P450 containing an Ir(Me)-PIX cofactor
Dydio, Pawel,Key, Hanna M.,Hayashi, Hiroki,Clark, Douglas S.,Hartwig, John F.
, p. 1750 - 1753 (2017)
Cytochrome P450 enzymes have been engineered to catalyze abiological C-H bond amination reactions, but the yields of these reactions have been limited by low chemoselectivity for the amination of C-H bonds over competing reduction of the azide substrate t
Discovery of novel DAPY-IAS hybrid derivatives as potential HIV-1 inhibitors using molecular hybridization based on crystallographic overlays
Huang, Boshi,Wang, Xueshun,Liu, Xinhao,Chen, Zihui,Li, Wanzhuo,Sun, Songkai,Liu, Huiqing,Daelemans, Dirk,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
, p. 4397 - 4406 (2017)
Crystallographic overlap studies and pharmacophoric analysis indicated that diarylpyrimidine (DAPY)-based HIV-1 NNRTIs showed a similar binding mode and pharmacophoric features as indolylarylsulfones (IASs), another class of potent NNRTIs. Thus, a novel series of DAPY-IAS hybrid derivatives were identified as newer NNRTIs using structure-based molecular hybridization. Some target compounds exhibited moderate activities against HIV-1 IIIB strain, among which the two most potent inhibitors possessed EC50 values of 1.48?μM and 1.61?μM, respectively. They were much potent than the reference drug ddI (EC50?=?76.0?μM) and comparable to 3TC (EC50?=?2.54?μM). Compound 7a also exhibited the favorable selectivity index (SI?=?80). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships, molecular modeling studies, and in silico calculation of physicochemical properties of these new inhibitors were also discussed.
Asymmetric synthesis of diarylmethyl amines by rhodium-catalyzed asymmetric addition of aryl titanium reagents to imines
Hayashi, Tamio,Kawai, Masahiro,Tokunaga, Norihito
, p. 6125 - 6128 (2004)
A rational tuning of the arene sulfonamide moiety (by introducing isopropyl groups onto the phenyl ring) brought about high enantioselectivity in the asymmetric synthesis of diarylmethyl amines by the title reaction (see scheme). Ar1 = 4-CF3C6H4, 4-ClC 6H4, 4-FC6H4, 3-MeOC 6H4, 4-MeOC6H4, 2-MeC 6H4, 1-naphthyl, Ph; Ar2 = Ph, 4-FC 6H4, 3-MeOC6H4, 4-MeOC 6H4.
Scandium triflate as an efficient and recyclable catalyst for the deprotection of tert-butyl aryl sulfonamides
Mahalingam,Wu, Xiongyu,Wan, Yiqian,Alterman, Mathias
, p. 417 - 425 (2005)
A mild and efficient method for deprotection of tert-butyl sulfonamide groups utilizing Sc(OTf)3 as deprotecting reagent has been developed. A variety of tert-butyl aryl sulfonamides used under these conditions gave the corresponding primary sulfonamides in high yields. The Lewis acid catalyst could be fully recovered and reused with maintained activity after the reactions. Copyright Taylor & Francis, Inc.
Mechanically Strong Heterogeneous Catalysts via Immobilization of Powderous Catalysts to Porous Plastic Tablets
Li, Tingting,Xu, Bo
supporting information, p. 2673 - 2678 (2021/08/03)
Main observation and conclusion: We describe a practical and general protocol for immobilization of heterogeneous catalysts to mechanically robust porous ultra-high molecular weight polyethylene tablets using inter-facial Lifshitz-van der Waals Interactions. Diverse types of powderous catalysts, including Cu, Pd/C, Pd/Al2O3, Pt/C, and Rh/C have been immobilized successfully. The immobilized catalysts are mechanistically robust towards stirring in solutions, and they worked well in diverse synthetic reactions. The immobilized catalyst tablets are easy to handle and reused. Moreover, the metal leaching of immobilized catalysts was reduced significantly.
