- Short Synthesis of Oxetane and Azetidine 3-Aryl-3-carboxylic Acid Derivatives by Selective Furan Oxidative Cleavage
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Four-membered rings remain underexplored motifs despite offering attractive physicochemical properties for medicinal chemistry. Arylacetic acids bearing oxetanes, azetidines, and cyclobutanes are prepared in two steps: a catalytic Friedel-Crafts reaction from four-membered ring alcohol substrates, followed by mild oxidative cleavage. The suitability of the products as building blocks is reflected in their facile purification and amenability to derivatization. Examples include heteroaromatics and aryltriflates, as well as oxetane-derived profen drug analogues and a new endomorphin derivative containing an azetidine amino acid residue.
- Bull, James A.,Choi, Chulho,Dubois, Maryne A. J.,Lee Wei Jie, Alvin,Mousseau, James J.,Smith, Milo A.,White, Andrew J. P.
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supporting information
p. 5279 - 5283
(2020/08/14)
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- Iridium-Catalyzed Enantioselective C(sp3)–H Borylation of Cyclobutanes
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We herein report the first example of iridium-catalyzed enantioselective C(sp3)–H borylation of cyclobutanes using benzoxazoline as the directing group. The combination of a chiral bidentate boryl ligand and an iridium precursor has found to effectively catalyze C(sp3)–H borylation to afford a variety of cyclobutylboronates with good to excellent enantioselectivities. We also demonstrate the synthetic utility of the current method by converting the stereogenic C—B bond to other functionalities.
- Chen, Xiang,Chen, Lili,Zhao, Hongliang,Gao, Qian,Shen, Zhenlu,Xu, Senmiao
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supporting information
p. 1533 - 1537
(2020/09/09)
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- Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)
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N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.
- He, Wu,Zhou, Bin,Liu, Weijia,Zhang, Meizi,Shen, Zhenhua,Han, Zhifu,Jiang, Qingwei,Yang, Qinghua,Song, Chuanjun,Wang, Ruiyong,Niu, Tianhui,Han, Shengna,Zhang, Lirong,Wu, Jie,Guo, Feima,Zhao, Renbin,Yu, Wenquan,Chai, Jijie,Chang, Junbiao
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p. 7341 - 7348
(2015/10/05)
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- A polar substituent effect on the ring-cleavage rearrangement of 1-arylcyclobutylmethyl Grignard reagents
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The kinetics of the ring-cleavage rearrangements of 1-phenylcyclobutylmethylmagnesium chloride and its p-methyl and p-chloro analogs have been determined.The first-order rate constants are correlated by the Hammett equation, with ρ=-0.47.The results are consistent with a concerted mechanism with a cyclic transition state having significant polar character, although polar effects on the stabilities of reactant and product may also contribute.The phenyl group itself slows the reaction by a factor of 0.031, which is interpreted principally in terms of steric destabilization of the transition state.
- Hill, E. Alexander,Li, Baoju
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- Therapeutic agents
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Compounds of formula I STR1 in which R1 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, cycloalkylalkyl or optionally substituted phenyl; R2 is H or C1-3 alkyl; R3 and/or R4 are H, formyl, C1-3 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-7 cycloalkyl or R3 and R4 together with the nitrogen atom form a heterocyclic ring system; R5 and/or R6 are H, halo, CF3, C1-3 alkyl, C1-3 alkoxy, C1-3 alkylthio or R5 and R6 together with the carbon atoms to which they are attached form a second benzene ring show therapeutic activity in the treatment of depression. Pharmaceutical compositions and processes for preparing compounds of formula I are disclosed.
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- Arylcyclobutylalkylamines and anti-depression composition and methods using same
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Compounds of formula I STR1 in which R1 is H or C1-3 alkyl; R2 is H or C1-3 alkyl; R3 and/or R4 are H, C1-3 alkyl, C3-6 alkenyl, C3-6 alkynyl, C3-7 cycloalkyl or R3 and R4 together with the nitrogen atom form a heterocyclic ring system; R5 and/or R6 are H, halo, CF3, or C1-3 alkyl (with the proviso that R5 and R6 cannot both be H or methyl) or R5 and R6 together with the carbon atoms to which they are attached form a second benzene ring and R7 and/or R8 are H or C1-3 alkyl show therapeutic activity in the treatment of depression. Pharmaceutical compositions and processes for preparing compounds of formula I are disclosed.
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- Insecticidal esters
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Compounds of the general formula I STR1 wherein R1 is hydrogen or a methoxy, ethoxy, propoxy, butoxy, tetrafluoroethoxy, methylthio, ethylthio, propylthio, fluoro, chloro, bromo, methyl, ethyl, or nitro group, and R2 is hydrogen or a methyl group, or R1 and R2 together form a methylenedioxy group; R3 is hydrogen, or a lower alkyl group, or one of the following groups (a) to (f): (a) 3-phenoxybenzyl (b) 2-benzyl-4-furylmethyl (c) α-cyano-3-phenoxybenzyl (d) 3,4-methylenedioxybenzyl (e) α-ethynyl-3-phenoxybenzyl (f) α-cyano-3-(4'-chlorophenoxy)-benzyl and Y1, Y2, Y3, Y4, Y5 and Y6 are the same or different groups and each is hydrogen or a fluoro, bromo or chloro group, with the proviso that when R1 is hydrogen, fluoro, chloro, bromo or methyl and R2 is hydrogen, then one of Y1 to Y6 is other than hydrogen. The compounds in which R3 is one of groups (a) to (f) are insecticides.
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- Insecticidal esters
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Compounds of the general formula I STR1 wherein R1 is hydrogen or a methoxy, ethoxy, propoxy, butoxy, tetrafluoroethoxy, methylthio, ethylthio, propylthio, fluoro, chloro, bromo, methyl, ethyl, or nitro group, and R2 is hydrogen or a methyl group, or R1 and R2 together form a methylenedioxy group; R3 is hydrogen, or a lower alkyl group, or one of the following groups (a) to (f): (a) 3-phenoxybenzyl (b) 2-benzyl-4-furylmethyl (c) α-cyano-3-phenoxybenzyl (d) 3,4-methylenedioxybenzyl (e) α-ethynyl-3-phenoxybenzyl (f) α-cyano-3-(4'-chlorophenoxy)-benzyl and Y1, Y2, Y3, Y4, Y5 and Y6 are the same or different groups and each is hydrogen or a fluoro, bromo or chloro group, with the proviso that when R1 is hydrogen, fluoro, chloro, bromo or methyl and R2 is hydrogen, then one of Y1 to Y6 is other than hydrogen. The compounds in which R3 is one of groups (a) to (f) are insecticides.
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