4830-05-1Relevant academic research and scientific papers
6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS
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Paragraph 0328; 0329, (2021/11/13)
The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.
(Cyclopentadienone)iron-Catalyzed Transfer Dehydrogenation of Symmetrical and Unsymmetrical Diols to Lactones
Tang, Yidan,Meador, Rowan I. L.,Malinchak, Casina T.,Harrison, Emily E.,McCaskey, Kimberly A.,Hempel, Melanie C.,Funk, Timothy W.
, p. 1823 - 1834 (2020/02/04)
Air-stable iron carbonyl compounds bearing cyclopentadienone ligands with varying substitution were explored as catalysts in dehydrogenative diol lactonization reactions using acetone as both the solvent and hydrogen acceptor. Two catalysts with trimethylsilyl groups in the 2- A nd 5-positions, [2,5-(SiMe3)2-3,4-(CH2)4(δ4-C4C= O)]Fe(CO)3 (1) and [2,5-(SiMe3)2-3,4-(CH2)3(δ4-C4C= O)]Fe(CO)3 (2), were found to be the most active, with 2 being the most selective in the lactonization of diols containing both primary and secondary alcohols. Lactones containing five-, six-, and seven-membered rings were successfully synthesized, and no over-oxidations to carboxylic acids were detected. The lactonization of unsymmetrical diols containing two primary alcohols occurred with catalyst 1, but selectivity was low based on alcohol electronics and modest based on alcohol sterics. Evidence for a transfer dehydrogenation mechanism was found, and insight into the origin of selectivity in the lactonization of 1°/2° diols was obtained. Additionally, spectroscopic evidence for a trimethylamine-ligated iron species formed in solution during the reaction was discovered.
Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones
Behrendt, Torsten,Erkel, Gerhard,Lucas, Tobias,Opatz, Till,Vierengel, Nina,Walter, Thorsten,Weber, Carina
, p. 5906 - 5917 (2020/08/19)
Through variation of our previously published total synthesis of two highly active anti-inflammatory macrolactones from the oxacyclododecindione family (J. Tauber, M. Rohr, T. Walter, G. Erkel and T. Opatz, Org. Biomol. Chem., 2015, 13, 7813-7821), seven new representatives of this compound class were prepared. Substitution of the 14-hydroxy group in oxacyclododecindione with a methyl substituent provided a readily accessible non-natural analogue which has similar pharmacological properties to the scarcely available natural product. Since the producible amount of substance is therefore no longer restricted by low fermentation yields, extensive in vivo studies become possible for the first time. Based on this finding, further investigations on structure-activity relationships were undertaken by variation of the halogen atom, which showed that exchange or omission of the chloro substituent led to significantly lower binding affinities. Furthermore, it was found that elongation of the crucial and characteristic aliphatic side chain at C-10 also increased the IC50 value in the biological assays of interest.
Catalyst-Controlled Diastereoselective Synthesis of Cyclic Amines via C-H Functionalization
Munnuri, Sailu,Adebesin, Adeniyi Michael,Paudyal, Mahesh P.,Yousufuddin, Muhammed,Dalipe, Alfonso,Falck, John R.
supporting information, p. 18288 - 18294 (2017/12/27)
Reliable regio- and stereochemical techniques applicable to nonactivated aliphatic systems remain largely elusive due to the challenges of discriminating between multiple, relatively strong sp3 C-H bonds whose chemical behavior often differ onl
Discovery of a flexible triazolylbutanoic acid as a highly potent uric acid transporter 1 (URAT1) inhibitor
Tian, He,Liu, Wei,Zhou, Zhixing,Shang, Qian,Liu, Yuqiang,Xie, Yafei,Liu, Changying,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
, (2016/12/02)
In order to systematically explore and understand the structure-activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH2, 18 compounds (1a-1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC50 = 0.23 μM against human URAT1 for 1q vs. 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity.
Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols
Xie, Xiaomin,Stahl, Shannon S.
supporting information, p. 3767 - 3770 (2015/04/14)
Cu/nitroxyl catalysts have been identified that promote highly efficient and selective aerobic oxidative lactonization of diols under mild reaction conditions using ambient air as the oxidant. The chemo- and regioselectivity of the reaction may be tuned by changing the identity of the nitroxyl cocatalyst. A Cu/ABNO catalyst system (ABNO = 9-azabicyclo[3.3.1]nonan-N-oxyl) shows excellent reactivity with symmetrical diols and hindered unsymmetrical diols, whereas a Cu/TEMPO catalyst system (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl) displays excellent chemo- and regioselectivity for the oxidation of less hindered unsymmetrical diols. These catalyst systems are compatible with all classes of alcohols (benzylic, allylic, aliphatic), mediate efficient lactonization of 1,4-, 1,5-, and some 1,6-diols, and tolerate diverse functional groups, including alkenes, heterocycles, and other heteroatom-containing groups.
PYRAZOLYL PYRROLINONES AND THEIR USE AS HERBICIDES
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Page/Page column 46-47, (2015/02/25)
The invention relates to pyrrolone compounds of the formula (I) wherein X, Ra, Rb, Rc, R1, R2 and R3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control plant growth.
PYRAZOLYL PYRROLINONES AND THEIR USE AS HERBICIDES
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Page/Page column 44, (2015/02/25)
The invention relates to pyrrolone compounds of the formula (I), wherein X, Ra, Rb, Rc, R1, R2 and R3 are as defined in the specification. Furthermore, the present invention relates to processes and intermediates for making compounds of formula (I), to herbicidal compositions comprising these compounds and to methods of using these compounds to control plant growth.
Mild and chemoselective synthesis of lactones from diols using a novel metal-ligand bifunctional catalyst.
Suzuki, Takeyuki,Morita, Kenji,Tsuchida, Mika,Hiroi, Kunio
, p. 2361 - 2363 (2007/10/03)
[reaction: see text] A novel amino alcohol-based Ir bifunctional complex acts as an efficient catalyst for oxidative lactonization of 1,4- or 1,5-diols with a substrate-to-catalyst molar ratio of 200-1000 in acetone or butanone. The reaction proceeds with broad functional group tolerance to give lactone in high yield at room temperature. The catalyst precursor Cp*IrCl[OCH(2)C(C(6)H(5))(2)NH(2)] is isolated and characterized by a single-crystal X-ray analysis.
Palladium(II)-catalyzed oxidation of alcohols to aldehydes and ketones by molecular oxygen
Nishimura, Takahiro,Onoue, Tomoaki,Ohe, Kouichi,Uemura, Sakae
, p. 6750 - 6755 (2007/10/03)
A novel combination of Pd(OAc)2/pyridine/MS3A catalyzes the aerobic oxidation in toluene of a variety of primary and secondary alcohols into the corresponding aldehydes and ketones in high yields. Various substituents and protecting groups are compatible with this oxidation. The ca. 2:3 ratio of O2 uptake to product yield is observed, whereas in the absence of MS3A, the ratio is ca. 1:1, suggesting the in situ formation of H2O2 and its decomposition by MS3A into water and oxygen. A catalytic cycle including the formation of a Pd(II)-alcoholate followed by β-elimination of a Pd(II)H species and a carbonyl compound and then the formation of a Pd(II)OOH species is proposed.
