98014-77-8Relevant academic research and scientific papers
NOVEL HISTONE METHYLTRANSFERASE INHIBITORS
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, (2021/04/01)
The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.
[Co(TPP)]-Catalyzed Formation of Substituted Piperidines
Lankelma, Marianne,Olivares, Astrid M.,de Bruin, Bas
supporting information, p. 5658 - 5663 (2019/04/08)
Radical cyclization via cobalt(III)-carbene radical intermediates is a powerful method for the synthesis of (hetero)cyclic structures. Building on the recently reported synthesis of five-membered N-heterocyclic pyrrolidines catalyzed by CoII porphyrins, the [Co(TPP)]-catalyzed formation of useful six-membered N-heterocyclic piperidines directly from linear aldehydes is presented herein. The piperidines were obtained in overall high yields, with linear alkenes being formed as side products in small amounts. A DFT study was performed to gain a deeper mechanistic understanding of the cobalt(II)-porphyrin-catalyzed formation of pyrrolidines, piperidines, and linear alkenes. The calculations showed that the alkenes are unlikely to be formed through an expected 1,2-hydrogen-atom transfer to the carbene carbon. Instead, the calculations were consistent with a pathway involving benzyl-radical formation followed by radical-rebound ring closure to form the piperidines. Competitive 1,5-hydrogen-atom transfer from the β-position to the benzyl radical explained the formation of linear alkenes as side products.
Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C-H Alkylation
Wang, Yong,Wen, Xin,Cui, Xin,Zhang, X. Peter
supporting information, p. 4792 - 4796 (2018/04/17)
Radical cyclization represents a powerful strategy for construction of ring structures. Traditional radical cyclization, which is based on radical addition as the key step, necessitates the use of unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C-H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)-H bonds. It allows for efficient construction of chiral pyrrolidines and other valuable 5-membered cyclic compounds. This alternative strategy of radical cyclization provides a new retrosynthetic paradigm to prepare five-membered cyclic molecules from readily available open-chain aldehydes through the union of C-H and C=O elements for C-C bond formation.
Asymmetric Syntheses of (-)-ADMJ and (+)-ADANJ: 2-Deoxy-2-amino Analogues of (-)-1-Deoxymannojirimycin and (+)-1-Deoxyallonojirimycin
Davies, Stephen G.,Figuccia, Aude L. A.,Fletcher Paul, Ai M.,Roberts,Thomson, James E.
, p. 6481 - 6495 (2016/08/16)
The asymmetric syntheses of (-)-ADMJ and (+)-ADANJ, the 2-deoxy-2-amino analogues of (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin, are described herein. Methodology for the ring-closing iodoamination of bishomoallylic amines followed by in situ ring-expansion (via intramolecular ring-opening of the corresponding aziridinium intermediates with a tethered carbamate moiety) to give oxazolidin-2-ones was initially optimized on a model system. Subsequent application of this methodology to two enantiopure bishomoallylic amines (which were produced via aminohydroxylation of an α,β-unsaturated ester, partial reduction, and reaction of the corresponding aldehyde with vinylmagnesium bromide) also proceeded with concomitant N-debenzylation to afford the corresponding diastereoisomerically pure (>99:1 dr) oxazolidin-2-ones. Subsequent deprotection of these enantiopure templates gave (-)-ADMJ and (+)-ADANJ as single diastereoisomers in 16% and 24% overall yield, respectively.
Metal-free, mild, nonepimerizing, chemo- and enantio- or diastereoselective N-alkylation of amines by alcohols via oxidation/imine-iminium formation/reductive amination: A pragmatic synthesis of octahydropyrazinopyridoindoles and higher ring analogues
Khan, Imran A.,Saxena, Anil K.
, p. 11656 - 11669 (2014/01/06)
A mild step and atom-economical nonepimerizing chemo- and enantioselective N-alkylating procedure has been developed via oxidation/imine-iminium formation/reduction cascade using TEMPO-BAIB-HEH-Bronsted acid catalysis in DMPU as solvent and a stoichiometric amount of amine. The optimized conditions were further extended for the nonenzymatic kinetic resolution of the chiral amine thus formed under nonenzymatic in situ hydrogen-transfer conditions using VAPOL-derived phosphoric acid (VAPOL-PA) as the Bronsted acid catalyst. The enantioselective cascade of the presented reaction was successfully utilized in the synthesis of octahydropyrazinopyridoindole and its higher ring analogues.
NOVEL COMPOUNDS USEFUL AS CC CHEMOKINE RECEPTOR LIGANDS
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Page/Page column 36, (2010/07/08)
The present invention relates to novel morpholine, oxazapane and piperidine derivatives that act as ligands for CC chemokine receptors, such as CCR1. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
8-Azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists
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Page/Page column 44-45, (2008/06/13)
The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.
[1,3]-Transfer of chirality during the nicholas reaction in γ-benzyloxy propargylic alcohols
Diaz, David D.,Ramirez, Miguel A.,Martin, Victor S.
, p. 2593 - 2606 (2008/02/07)
A highly regio- and stereoselective intramolecular [1.5]-hydrogentransfer process is described. Treatment of γ-benzyl-protccted Co 2(CO)6-α,γ-acetylenic diols with BF 3·OEt2 provides bis-homopropargylic alcohols. The reaction occurs within seconds, tolerates a wide range of functionalities, and provides good yields. When the ether group is located at a stereochemically defined carbon atom, the rearrangement occurs with high stereoselectivity, transferring the chirality of the carbinol center to the newly created stereocenter. The cleavage of the benzyloxy group is totally regioselective when additional benzyl ethers are present. The scope and limitations of this novel process in densely substituted substrates are evaluated, and possible competitive reactions and/or stereochemical influences are also described. A mechanism based on a highly ordered chair-like transition state substantiated by a theoretical study is also included.
Pyrimidinone-1,3-oxathiolane derivatives with antiviral activity
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, (2008/06/13)
Compounds of formula (I) wherein Ra and Rb the same or different, are hydrogen atoms, acyl groups deriving from a lower carboxylic acid or chains of formula (a) useful as reverse transcriptase inhibitors antiviral activity are described.
Enantioselective synthesis of 1,2-, 1,3- and 1,4- aminoalcohols by the addition of dialkylzincs to 1,2-, 1,3- and 1,4- aminoaldehydes
Lutz, Christian,Lutz, Volker,Knochel, Paul
, p. 6385 - 6402 (2007/10/03)
Chiral 1,3- and 1,4- aminoalcohols were prepared by the addition of functionalized dialkylzincs to 1,3-aliphatic and 1,4-unsaturated aminoaldehydes with good to excellent enantioselectivity. Syn- or anti-1,2- aminoalcohols are stereoselectively obtained by asymmetric addition of dialkylzincs to α-aminoaldehydes depending on the choice of the chiral catalyst. A chelate controlled addition is observed if less than stoichiometric amounts of Ti(Oi-Pr)4 are used.
