- Borocyclopropanation of Styrenes Mediated by UV-light Under Continuous Flow Conditions
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Herein, we report a user-friendly and metal-free UV-A light mediated borocyclopropanation of styrenes using continuous flow technology. A broad range of styrene derivatives can be cyclopropanated in good yields within 1 h residence time to produce highly
- Sayes, Morgane,Benoit, Guillaume,Charette, André B.
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- Synthesis of Borylcyclopropanes by Chromium-Promoted Cyclopropanation of Unactivated Alkenes
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The combination of diiodomethylboronate ester, CrCl2 with TMEDA promoted borylcyclopropanation of unactivated alkenes under mild conditions. Compared with the typical Simmons-Smith cyclopropanation, the current protocol offers the following adv
- Murai, Masahito,Mizuta, Chisato,Taniguchi, Ryuji,Takai, Kazuhiko
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Read Online
- Design, synthesis, and biological evaluation of novel 2′-methyl-2′-fluoro-6-methyl-7-alkynyl-7-deazapurine nucleoside analogs as anti-Zika virus agents
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Zika virus (ZIKV) is a mosquito-borne flavivirus and outbreaks of ZIKV have been reported in Africa, Americas and other parts of the world lately. The ZIKV epidemic has received extensive attention due to its ability to cause serious medical consequences and complications such as microcephaly and Guillain-Barre syndrome in recent years. Up to now, there are no specific treatments or vaccines available for ZIKV infection, which highlights the urgent need for developing new therapies. In this work, we designed and synthesized a series of novel 6-methyl-7-acetylenenyl-7-deazapurine nucleoside analogs as potential inhibitors of ZIKV replication. The biological activities against ZIKV replication were evaluated and the structure-activity relationship (SAR) was also studied. Among the compounds evaluated, nucleoside analog 38 (EC50 = 2.8 ± 0.8 μM, EC90 = 6.8 ± 2.3 μM) showed the most potent anti-ZIKV activity with low cytotoxicity (CC50 = 54.1 ± 6.9 μM) in an A549 based cellular model. The inhibitory activity of 38 was about 5 times more potent than the positive control NITD008. Notably, 38 showed similar inhibition potency against different ZIKV strains (ZG-01 and MR766) in a variety of host cell types including SNB19, A549, Huh7, Vero. In addition, 38 (Kd = 1.87 μM) has a stronger affinity to ZIKV RNA-dependent RNA polymerase (RdRp) protein than NITD008 (Kd = 3.43 μM) in the non-phosphorylation assay. These results indicated that compound 38 may serve as a promising candidate in future anti-ZIKV drug discovery.
- Yao, Guoqiang,Yu, Jianchen,Lin, Cai,Zhu, Yujia,Duan, Anna,Li, Mengfeng,Yuan, Jie,Zhang, Jiancun
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supporting information
(2022/03/23)
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- SHP2 INHIBITORS, COMPOSITIONS AND USES THEREOF
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Provided are compounds of Formula (I), methods of using the compounds as SHP2 inhibitors, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating SHP2-mediated diseases.
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- Electrochemically promoted decarboxylative borylation of alkyl N-hydroxyphthalimide esters
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An electrochemically promoted decarboxylative borylation reaction is reported. The reaction proceeds under mild conditions in an undivided cell without use of transition metal- or photo-catalysts. The key feature of the reaction is the compatibility of di
- Dai, Jian-Jun,Fang, Wen,Teng, Xin-Xin,Xu, Hua-Jian,Xu, Jun
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- Method for rapidly preparing cyclopropane derivative based on microchannel reaction technology
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The invention discloses a method for rapidly preparing a cyclopropane derivative based on a microchannel reaction technology, which comprises an alkaline hydrolysis reaction and an electrophilic addition reaction. The alkaline hydrolysis reaction comprise
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Paragraph 0050-0052
(2021/08/06)
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- Reductive Ring-Opening 1,3-Difunctionalizations of Arylcyclopropanes with Sodium Metal
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Sodium dispersion promotes reductive ring opening of arylcyclopropanes. The presence of a reduction-resistant electrophile, such as methoxypinacolatoborane, epoxide, oxetane, paraformaldehyde, or chlorotrimethylsilane, during the reductive ring opening event leads to the formation of 1,3-difunctionalized 1-arylalkanes by immediate trappings of the resulting two reactive carbanions. In particular, the ring-opening 1,3-diborylations of arylcyclopropanes afford 1,3-diborylalkanes with high syn selectivity.
- Wang, Shuo,Kaga, Atsushi,Yorimitsu, Hideki
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supporting information
p. 219 - 223
(2020/11/04)
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- Stereoselective Functionalization of Racemic Cyclopropylzinc Reagents via Enantiodivergent Relay Coupling
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Efficient construction of optically pure molecules from readily available starting materials in a simple manner is an ongoing goal in asymmetric synthesis. As a straightforward route, transition-metal-catalyzed enantioconvergent coupling between widely available secondary alkyl electrophiles and organometallic nucleophiles has emerged as a powerful strategy to construct chiral center(s). However, the scope of racemic secondary alkylmetallic nucleophiles for this coupling remains limited in specific substrates because of the difficulties in stereoselective formation of the key alkylmetal intermediates. Here, we report an enantiodivergent strategy to efficiently achieve an array of synthetically useful chiral cyclopropanes, including chiral fluoroalkylated cyclopropanes and enantiomerically enriched cyclopropanes with chiral side chains, from racemic cyclopropylzinc reagents. This strategy relies on a one-pot, two-step enantiodivergent relay coupling process of the racemic cis-cyclopropylzinc reagents with two different electrophiles, which involves kinetic resolution of racemic cis-cyclopropylzinc reagents through a nickel-catalyzed enantioselective coupling with alkyl electrophiles, followed by a stereospecific relay coupling of the remaining enantiomeric cyclopropylzinc reagent with various electrophiles, to produce two types of functionalized chiral cyclopropanes with opposite configurations on the cyclopropane ring. These chiral cyclopropanes are versatile synthons for diverse transformations, rendering this strategy effective for obtaining structurally diversified molecules of medicinal interest.
- An, Lun,Tong, Fei-Fei,Zhang, Shu,Zhang, Xingang
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supporting information
p. 11884 - 11892
(2020/08/06)
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- Decarboxylative Borylation of mCPBA-Activated Aliphatic Acids
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A decarboxylative borylation of aliphatic acids for the synthesis of a variety of alkylboronates has been developed by mixing m-chloroperoxybenzoic acid (mCPBA)-activated fatty acids with bis(catecholato)diboron in N,N-dimethylformamide (DMF) at room temperature. A radical chain process is involved in the reaction which initiates from the B-B bond homolysis followed by the radical transfer from the boron atom to the carbon atom with subsequent decarboxylation and borylation.
- Wei, Dian,Liu, Tu-Ming,Zhou, Bo,Han, Bing
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p. 234 - 238
(2020/01/02)
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- H2-Acceptorless Dehydrogenative Boration and Transfer Boration of Alkenes Enabled by Zirconium Catalyst
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The first example of an efficient and direct dehydrogenative boration of alkenes for vinyl boronate ester synthesis was achieved using a zirconium catalyst. Our methodology avoids using precious transition metals, additional hydrogen acceptors, high temperatures, and long reaction times, which were required to overcome the reducing ability of borane, to give alkyl boronate esters. Detailed mechanistic studies revealed a reversible reaction pathway and further suggested applying the zirconium complex as a “shuttle catalyst” for transfer boration, which thus sidesteps the use of relatively sensitive borane.
- Shi, Xiaonan,Li, Sida,Wu, Lipeng
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p. 16167 - 16171
(2019/11/03)
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- Cu-Catalyzed Decarboxylative Borylation
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A simple method for the conversion of carboxylic acids to boronic esters via redox-active esters (RAEs) is reported using copper catalysis. The scope of this transformation is broad, and compared with the known protocols available, it represents the most inexpensive, rapid, and operationally simple option. In addition to a full exploration of the scope, a kinetic study was performed to elucidate substrate and reagent concentration dependences.
- Wang, Jie,Shang, Ming,Lundberg, Helena,Feu, Karla S.,Hecker, Scott J.,Qin, Tian,Blackmond, Donna G.,Baran, Phil S.
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p. 9537 - 9542
(2018/09/27)
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- CU-AND NI-CATALYZED DECARBOXYLATIVE BORYLATION REACTIONS
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The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(ll) salt or a copper salt, and an Mg(ll) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.
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Page/Page column 27; 33-34; 35; 36; 40; 43; 70; 77
(2018/10/19)
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- Method for preparing cyclopropyl boric acid ester compound on basis of iron catalysis
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The invention relates to a method for preparing a cyclopropyl borate compound on the basis of iron catalysis, and belongs to the field of compound preparation. The method for preparing the cyclopropylborate compound on the basis of iron catalysis is chara
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Paragraph 0053; 0060-0062; 0114-0155
(2019/09/10)
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- METHODS FOR PREPARING A BORONIC ACID OR A BORONIC ESTER
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Methods are disclosed for converting a carboxylic acid by using a diboron reagent to convert the carboxylic acid or imide ester derivative of a carboxylic acid to a boronic ester. The method may involve providing an imide ester, such as a phthalimide ester, of a carboxylic acid, and treating the imide ester with a diboron reagent, thereby forming a boronic ester. The diboron reagent may be selected from bis(catecholato)diboron, B2(OH)4 or a mixture thereof, optionally in the presence of catechol.
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Page/Page column 5; 8-9; 24-25
(2018/11/10)
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- A Copper Catalyst with a Cinchona-Alkaloid-Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes
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A copper-catalyzed asymmetric radical oxytrifluoromethylation of alkenyl oxime and Togni's reagent has been successfully developed, thereby providing straightforward access to CF3-containing isoxazolines bearing α-tertiary stereocenters with excellent yield and enantioselectivity. The key to success is the rational design of cinchona-alkaloid-based sulfonamides as neutral/anionic hybrid ligands to effectively control the stereochemistry in copper-catalyzed reactions involving free alkyl radical species. The utility of this method is illustrated by efficient transformation of the products into useful chiral CF3-containing 1,3-aminoalcohols.
- Li, Xi-Tao,Gu, Qiang-Shuai,Dong, Xiao-Yang,Meng, Xiang,Liu, Xin-Yuan
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p. 7668 - 7672
(2018/05/30)
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- Diastereoselective borocyclopropanation of allylic ethers using a boromethylzinc carbenoid
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A borocyclopropanation of (E)- and (Z)-allylic ethers and styrene derivatives via the Simmons-Smith reaction using a novel boromethylzinc carbenoid is described. The carbenoid precursor is prepared via a 3-step sequence from inexpensive and commercially available starting materials. This methodology allows for the preparation of 1,2,3-substituted borocyclopropanes in high yields and diastereoselectivities. Several postfunction-alization reactions were also performed to illustrate the versatility of these building blocks.
- Benoit, Guillaume,Charette, André B.
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supporting information
p. 1364 - 1367
(2017/02/10)
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- One-Pot, Three-Step Synthesis of Cyclopropylboronic Acid Pinacol Esters from Synthetically Tractable Propargylic Silyl Ethers
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Simple propargylic silyl ethers can be converted to complex cyclopropylboronic acid pinacol esters in an efficient one-pot procedure. Terminal acetylenes undergo a Schwartz's reagent catalyzed hydroboration; subsequent addition of further Schwartz's reage
- Spencer, Jonathan A.,Jamieson, Craig,Talbot, Eric P. A.
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p. 3891 - 3894
(2017/07/26)
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- Photoinduced decarboxylative borylation of carboxylic acids
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The conversion of widely available carboxylic acids into versatile boronic esters would be highly enabling for synthesis. We found that this transformation can be effected by illuminating the N-hydroxyphthalimide ester derivative of the carboxylic acid under visible light at room temperature in the presence of the diboron reagent bis(catecholato)diboron. A simple workup allows isolation of the pinacol boronic ester. Experimental evidence suggests that boryl radical intermediates are involved in the process. The methodology is illustrated by the transformation of primary, secondary, and tertiary alkyl carboxylic acids as well as a diverse range of natural-product carboxylic acids, thereby demonstrating its broad utility and functional group tolerance.
- Fawcett, Alexander,Pradeilles, Johan,Wang, Yahui,Mutsuga, Tatsuya,Myers, Eddie L.,Aggarwal, Varinder K.
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p. 283 - 286
(2017/07/27)
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- Decarboxylative borylation
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The widespread use of alkyl boronic acids and esters is frequently hampered by the challenges associated with their preparation.We describe a simple and practical method to rapidly access densely functionalized alkyl boronate esters from abundant carboxylic substituents. This broad-scope nickel-catalyzed reaction uses the same activating principle as amide bond formation to replace a carboxylic acid moiety with a boronate ester. Application to peptides allowed expedient preparations of a-amino boronic acids, often with high stereoselectivity, thereby facilitating synthesis of the alkyl boronic acid drugs Velcade and Ninlaro as well as a boronic acid version of the iconic antibiotic vancomycin. The reaction also enabled the discovery and extensive biological characterization of potent human neutrophil elastase inhibitors, which offer reversible covalent binding properties.
- Li, Chao,Wang, Jie,Barton, Lisa M.,Yu, Shan,Tian, Maoqun,Peters, David S.,Kumar, Manoj,Yu, Antony W.,Johnson, Kristen A.,Chatterjee, Arnab K.,Yan, Ming,Baran, Phil S.
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- Automated library synthesis of cyclopropyl boronic esters employing diazomethane in a tube-in-tube flow reactor
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The efficient synthesis of cyclopropyl boronic esters in library format using a diazomethane flow reactor has been achieved. A pivotal component of the system is a fully automated tube-in-tube reactor allowing for safe handling of hazardous diazomethane on repeated small scale and for the generation of larger quantities of product. The setup enables the repeated execution of Pd-catalyzed cyclopropanation reactions without compromising its operation over time.
- Koolman, Hannes F.,Kantor, Stanislaw,Bogdan, Andrew R.,Wang, Ying,Pan, Jeffrey Y.,Djuric, Stevan W.
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supporting information
p. 6591 - 6595
(2016/07/16)
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- Exploiting the enantioselectivity of Baeyer-Villiger monooxygenases via boron oxidation
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The enantioselective carbon-boron bond oxidation of several chiral boron-containing compounds by Baeyer-Villiger monooxygenases was evaluated. PAMO and M446G PAMO conveniently oxidized 1-phenylethyl boronate into the corresponding 1-(phenyl)ethanol (ee = 82-91%). Cyclopropyl boronic esters were also oxidized but with no enantioselectivity. β-Boryl carboxylic esters were not oxidized by any BVMOs.
- Brondani, Patricia B.,Dudek, Hanna,Reis, Joel S.,Fraaije, Marco W.,Andrade, Leandro H.
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scheme or table
p. 703 - 708
(2012/09/21)
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- Enantioselective synthesis of trans-aryl-and-heteroaryl-substituted cyclopropylboronates by copper (I)-catalyzed reactions of allylic phosphates with a diboron derivative
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A new asymmetric route for the synthesis of trans-2-aryl- and -heteroaryl-substituted cyclopropylboronates has been developed. (Z)-3-arylallylic phosphates were converted to the optically active products with high yield and diastereo- and enantioselectivity through a copper(I)-catalyzed reaction with a diboron derivative. Under mild reaction conditions, the reaction affords the arylcyclopropane products with a functional group and a heteroaromatic group in a highly enantioselective manner. When (E)-allylic phosphates were used as substrates, a ligand-controlled product switch between the trans and cis configurations was observed.
- Zhong, Chongmin,Kunii, Shun,Kosaka, Yuki,Sawamura, Masaya,Ito, Hajime
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supporting information; experimental part
p. 11440 - 11442
(2010/10/04)
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- MANUFACTURING METHOD OF ORGANOBORON COMPOUND
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A manufacturing method for one of, or a mixture of, an optically active allylboron compound and racemic or optically active boryl cyclopropane, including a coupling reaction, in the presence of a catalyst, between allyl compound and diboron compound. It i
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Page/Page column 12
(2008/12/04)
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- INDOLES USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I), Wherein X1 , R1 , R2 , R3, R4, R5 and R6 have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a member of the MAPEG family is desired and/or required, and particularly in the treatment of inflammation.
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Page/Page column 122
(2008/06/13)
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- Kinetic Enzymatic Resolution of Cyclopropane Derivatives
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The kinetic enzymatic resolution of various cyclopropane derivatives was systematically investigated. The study focused on synthetically useful cyclopropylmethanols (e.g., 18a/j or 19a/j) as well as some rarely investigated cyclopropanols (e.g., 24/25 or 27). The combination of enantioselective catalytic or diastereoselective synthesis of enantiomerically enriched compounds with enzymatic approaches ultimately led to the most convenient route to enantiomerically pure starting materials. Again, this was especially proven for the synthesis of cyclopropanols 18a/j and 19a/j. Key to the successful investigation was to rigorously establish an analytical tool for the analysis of enantiomeric composition of reaction mixtures.
- Pietruszka, Joerg,Rieche, Anja C. M.,Wilhelm, Thorsten,Witt, Andreas
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p. 1273 - 1286
(2007/10/03)
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