- Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
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Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
- Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
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supporting information
p. 2707 - 2713
(2020/03/30)
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- One-Pot Synthesis of 2,5-Disubstituted Furans through In Situ Formation of Allenes and Enolization Cascade
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A one-pot synthesis of 2,5-disubstituted furans from γ-ketoacids is reported. In situ formation of allenoates by action of chloroformate on carboxylic acid following by enolization of ketone affords furan derivatives by cyclization. The reaction was extended to a wide scope of ketoacids and phosphonium salts. This methodology was applied on levulinic acid and derivatives, one of the biosourced platform chemicals.
- Bernhard, Yann,Gilbert, Joachim,Bousquet, Till,Favrelle-Huret, Audrey,Zinck, Philippe,Pellegrini, Sylvain,Pelinski, Lydie
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supporting information
p. 7870 - 7873
(2019/12/24)
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- Nickel-Catalyzed Desymmetrizing Cross-Electrophile Coupling of Cyclic Meso-Anhydrides
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A Ni-catalyzed desymmetrizing cross-electrophile coupling of cyclic meso-anhydrides with aryl triflates has been successfully demonstrated. This is the only example using cyclic meso-anhydrides in cross-electrophile coupling reactions. A diverse array of valuable γ-keto acid building blocks can be generated under these conditions with excellent functional group tolerance and stereochemical fidelity.
- Lin, Tingzhi,Mi, Jianjun,Song, Lichao,Gan, Jiamin,Luo, Pan,Mao, Jianyou,Walsh, Patrick J.
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supporting information
p. 1191 - 1194
(2018/02/22)
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- DOUBLE-ACYLATED GLP-1 DERIVATIVES
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The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1 (7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1 (7-37), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37), wherein the first K residue is designated K37, and the second K residue is designated K26, which derivative comprises two albumin binding moieties attached to K26 and K37, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: ????????Chem. 1:?????HOOC-(CH2)x-CO-* ????????Chem. 2:?????HOOC-C6H4-O-(CH2)y-CO-* ????????Chem. 3:?????R1-C6H4-(CH2)z-CO-* ????????Chem. 4:?????HOOC-C4SH2-(CH2)w-CO-* in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, R1 is a group having a molar mass not higher than 150 Da, and w is an integer in the range of 6-18; with the proviso that when the protracting moiety is Chem. 1, the albumin binding moiety further comprises a linker of formula Chem. 5: *-NH-(CH2)2-(O-(CH2)2)k-O-(CH2)n-CO-*, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
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Paragraph 0268
(2016/07/27)
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- Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones
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Sixteen new 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2 H)-ones (2a-p) were synthesized and tested for in vitro anticancer and in vivo anti-inflammatory activities. Eleven (2b, 2d , 2-ej and 2m-p) of the obtained compounds were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Compound 2f showed remarkable activity with GI50 less than 1 μM on 36 human tumor cell lines and has been referred to Biological Evaluation Committee (NCI) for advance study. Compound 2g also displayed promising antiproliferative activity against 20 different cell lines with GI50 less than 1 μM. Compounds 2k and 2n were found to have a comparable anti-inflammatory activity to that of standard drug etoricoxib in carrageenan-induced rat hind paw edema model at 5 h.
- Ovais, Syed,Javed, Kalim,Yaseen, Shafiya,Bashir, Rafia,Rathore, Pooja,Yaseen, Raed,Hameed, Alhamzah D.,Samim, Mohammad
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p. 352 - 358
(2013/10/01)
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- SYNTHESIS OF SUBSTITUTED TETRAHYDROINDENYL COMPLEXES
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This invention relates to the synthesis of substituted tetrahydroindenyls and the use of the synthesised complexes in the homo- and co-polymerisation of ethylene and alpha-olefins.
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Page/Page column 13-15
(2010/08/04)
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- Oxetanes in drug discovery: Structural and synthetic insights
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An oxetane can trigger profound changes in aqueous solubility, lipophilicity, metabolic stability, and conformational preference when replacing commonly employed functionalities such as gem-dimethyl or carbonyl groups. The magnitude of these changes depends on the structural context. Thus, by substitution of a gem-dimethyl group with an oxetane, aqueous solubility may increase by a factor of 4 to more than 4000 while reducing the rate of metabolic degradation in most cases. The incorporation of an oxetane into an aliphatic chain can cause conformational changes favoring synclinal rather than antiplanar arrangements of the chain. Additionally spirocyclic oxetanes (e.g., 2-oxa-6-aza-spiro[3.3]heptane) bear remarkable analogies to commonly used fragments in drug discovery, such as morpholine, and are even able to supplant the latter in its solubilizing ability. A rich chemistry of oxetan-3-one and derived Michael acceptors provide venues for the preparation of a broad variety of novel oxetanes not previously documented, thus providing the foundation for their broad use in chemistry and drug discovery.
- Wuitschik, Georg,Carreira, Erick M.,Wagner, Bj?rn,Fischer, Holger,Parrilla, Isabelle,Schuler, Franz,Rogers-Evans, Mark,Müller, Klaus
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supporting information; experimental part
p. 3227 - 3246
(2010/08/19)
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- OXAZOLIDINONE DERIVATIVES, PROCESS FOR THEIR PREPERATION AND THEIR USE AS ANTIMYCOBACTERIAL AGENTS
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Novel compounds belonging to the class of oxazolidinones possessing potent antimycobacterial properties especially useful in the treatment of acid fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium-intracellular complex, M. fortuitum and M. kansai. The compound and its pharmaceutically acceptable salts thereof act as antibacterial agents. Also disclosed is a method for inhibiting growth of mycobacterial cells a well as a method of treating mycobacterial conditions such as Mycobacterium tuberculoses, drug resistant Mycobacterium tuberculosis, Mycobacterium avium-intracellular complex, M. fortuitum and M. kansai, comprising administering an antimycobacterially effective amount of the said compound and/or pharmaceutically acceptable salts thereof. There is also disclosed a process for the manufacture of the said compound or its pharmaceutically acceptable salts.
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- Phosphonic acid compounds, their production and use
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The present invention relates to a compound of the general formula (I): STR1 wherein ring A is a benzene ring that may be substituted; Y is a divalent group as a constituent member of ring B forming a 5- to 8-membered ring; Q1 is a group of the formula --X--P(O)(OR1)(OR2) wherein X is a bond or a divalent group; R1 and R2, identical or different, are hydrogen or a lower alkyl, or may be combined together to form a ring; Q2 is hydrogen, a hydrocarbon group that may be substituted or a heterocyclic group that may be substituted; and the group of the formula --CON(Q1)(Q2) is connected to the a- or b-position carbon atom, or a salt thereof, which is useful as prophylactic and therapeutic agents of various metabolic bone diseases such as osteoporosis.
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- Process for the production of cyclic sulfonium salts
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A process for the production of a 5-7 membered ring cyclic sulfonium salt compound, including a 5-7 membered ring cyclic sulfonium salt compound having a non-nucleophilic anion, is described. Members of the latter group are potentially useful as initiators for cationic polymerizations. The process comprises reacting a 1.4-, 1.5-, or 1.6-diol compound or a 5-7 membered ring cyclic ether compound with a mercapto compound and a strong protonic acid yielding the cyclic sulfonium salt compound. Some compounds described are also novel compounds per se.
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- Electron Paramagnetic Resonance Spectra of Substituted 1- and 2-Naphthylmethyl Radicals
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The EPR spectra of 7-tert-butyl-1-naphthylmethyl and 6-tert-butyl-2-naphthylmethyl radicals, prepared by photolysis of the hydrocarbon with tert-butyl peroxide at -40 deg C, have been analysed by correlation methods: average α(C-H) coupling constants are 15.0 and 15.25 G respectively, in line with the expected relative stabilities of the two radicals and the recently reported stabilization energy for 1-naphthylmethyl.
- Jackson, Richard A.,Rhodes, Christopher J.
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- Chemical process for the preparation of esters of substituted cyclopropyl caboxylic acids
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A process for the preparation of a compound of the general formula (III): wherein R1, R2, R5 and R6 each represent a hydrogen atom or an alkyl group containing from l to 4 carbon atoms, R is an alkyl group and X and Y each represent
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- SUBSTITUTED THIO-SUBSTITUTED BENZYL-PROPIONYL-L-PROLINES
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This disclosure describes novel substituted ω-aroyl(propionyl or butyryl)-L-prolines and the esters and cationic salts thereof which are useful as hypotensive agents in mammals.
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