- Stereodivergence in the Ireland-Claisen Rearrangement of α-Alkoxy Esters
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A systematic investigation into the Ireland-Claisen rearrangement of α-alkoxy esters is reported. In all cases, the use of KN(SiMe3)2 in toluene gave rearrangement products corresponding to a Z-enolate intermediate with excellent diastereoselectivity, presumably because of chelation control. On the other hand, chelation-controlled enolate formation could be overcome for most substrates through the use of lithium diisopropylamide (LDA) in tetrahydrofuran (THF).
- Podunavac, Ma?a,Lacharity, Jacob J.,Jones, Kerry E.,Zakarian, Armen
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supporting information
p. 4867 - 4870
(2018/08/24)
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- Discovery of novel 20S proteasome inhibitors by rational topology-based scaffold hopping of bortezomib
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A series of structurally novel proteasome inhibitors 1–12 have been developed based rational topology-based scaffold hopping of bortezomib. Among these novel proteasome inhibitors, compound 10 represents an important advance due to the comparable proteasome-inhibitory activity (IC50 = 9.7 nM) to bortezomib (IC50 = 8.3 nM), the remarkably higher BEI and SEI values and the effectiveness in metabolic stability. Therefore, compound 10 provides an excellent lead suitable for further optimization.
- Xu, Yulong,Yang, Xicheng,Chen, Yiyi,Chen, Hao,Sun, Huijiao,Li, Wei,Xie, Qiong,Yu, Linqian,Shao, Liming
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p. 2148 - 2152
(2018/05/25)
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- Boric acid compound used as 20S proteasome inhibitor, and preparation method thereof
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The invention relates to the fields of pharmaceutical chemistry and medicine therapeutics, concretely relates to new boric acid compounds, and a preparation method and a use thereof, and especially relates to a boric acid compound used as a 20S proteasome inhibitor, and a preparation method thereof. The invention also discloses a boric acid compound represented by formula I, and a preparation method thereof. A result of bioactive screening test shows that the compound prepared in the invention has a proteasome inhibition function, and can be further used for preparing medicines for treating proteasome correlated diseases.
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- NEUROPEPTIDE S RECEPTOR (NPSR) AGONISTS
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Neuropeptide S receptor agonists are provided. The NPS agonists include peptidomimetic analogs exhibiting affinity for and activity at the neuropeptide S receptor. The molecules may be useful in the treatment of disorders, syndromes and conditions mediated by modulation of the neuropeptide S receptor such as substance abuse, narcolepsy, insomnia, obesity, cognitive decline, dementia, Alzheimer's disease, panic disorder, generalized anxiety, PTSD, phobias, schizophrenia and as supportive medication during any kind of cessation program in cognitive behavioral therapy, such as drug addiction, eating disorders and gambling.
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Paragraph 000103; 000126
(2017/11/04)
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- Novel iridium complex of spirophosphine-carboxylic acid, preparation method and application thereof
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The invention relates to an iridium complex of spirophosphine-carboxylic acid, a preparation method and application thereof. The iridium complex of spirophosphine-carboxylic acid is a compound with a structure shown as formula (I), wherein n=0-3; and the values of R1, R2, R3, R4, R5, R6 and R7 are defined as claim 1. Substituted 7-carboxyl-7'-diarylphosphino-1, 1'-spirobiindane is taken as the ligand to from carboxylic acid anion under the action of alkali, and then complexation with an iridium precursor is carried out to obtain different iridium/spirophosphine-carboxylic acid complexes. The iridium complex of spirophosphine-carboxylic acid provided by the invention can catalyze the asymmetric hydrogenation reaction of a variety of unsaturated carboxylic acids, and show high activity and enantioselectivity, thus having good industrialization prospects. (formula (I)).
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Paragraph 0081-0085
(2017/05/20)
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- Neutral iridium catalysts with chiral phosphine-carboxy ligands for asymmetric hydrogenation of unsaturated carboxylic acids
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We developed neutral iridium catalysts with chiral spiro phosphine-carboxy ligands (SpiroCAP) for asymmetric hydrogenation of unsaturated carboxylic acids. Different from the cationic Crabtree-type catalysts, the iridium catalysts with chiral spiro phosphine-carboxy ligands are neutral and do not require the use of a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF?) counterion, which is necessary for stabilizing cationic Crabtree-type catalysts. Another advantage of the neutral iridium catalysts is that they have high stability and have a long lifetime in air. The new iridium catalysts with chiral spiro phosphine-carboxy ligands exhibit unprecedented high enantioselectivity (up to 99.4% ee) in the asymmetric hydrogenations of various unsaturated carboxylic acids, particularly for 3-alkyl-3-methylenepropionic acids, which are challenging substrates for other chiral catalysts.
- Yang, Shuang,Che, Wen,Wu, Hui-Ling,Zhu, Shou-Fei,Zhou, Qi-Lin
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p. 1977 - 1980
(2017/03/09)
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- Asymmetric hydrogenation method of alpha-oxo-alpha, beta-unsaturated carboxylic acid
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The invention relates to an asymmetric hydrogenation method of alpha-oxo-alpha, beta-unsaturated carboxylic acid. A metal complex containing ChenPhos chiral ligand is a catalyst high in conversion efficiency, and particularly, the catalyst can be used for
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Paragraph 0023; 0024; 0025; 0026
(2016/10/09)
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- Highly enantioselective hydrogenation of α-oxy functionalized α,β-unsaturated acids catalyzed by a ChenPhos-Rh complex in CF3CH2OH
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Rhodium complexes coordinated by Chenphos are very effective catalysts for the enantioselective hydrogenation of α-aryloxy- and α-alkoxy-substituted α,β-unsaturated carboxylic acids under mild conditions in CF3CH2OH. The catalytic system could be successfully employed in building the core structure of a new FDA approved drug LCZ 696.
- Yao, Lin,Wen, Jialin,Liu, Shaodong,Tan, Renchang,Wood, Noel Marie,Chen, Weiping,Zhang, Shengyong,Zhang, Xumu
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supporting information
p. 2273 - 2276
(2016/02/18)
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- Enantioselective hydrogenation of α-substituted acrylic acids catalyzed by iridium complexes with chiral spiro aminophosphine ligands
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Highly active: Iridium complexes with chiral spiro aminophosphine ligands were synthesized and applied as catalysts for the asymmetric hydrogenation of α-substituted acrylic acids (see scheme). The complexes were highly active catalysts, showing turnover frequencies of up to 6000 h-1, and catalyst loadings could be reduced to 0.01 mol %. Copyright
- Zhu, Shou-Fei,Yu, Yan-Bo,Li, Shen,Wang, Li-Xin,Zhou, Qi-Lin
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supporting information; experimental part
p. 8872 - 8875
(2012/10/08)
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- Enantioselective hydrogenation of α-aryloxy and α-alkoxy α,β-unsaturated carboxylic acids catalyzed by chiral spiro iridium/phosphino-oxazoline complexes
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The iridium-catalyzed highly enantioselective hydrogenation of α-aryloxy and α-alkoxy-substituted α,β-unsaturated carboxylic acids was developed. By using chiral spiro phosphino-oxazoline ligands, the hydrogenation proceeded smoothly to produce various α-aryloxy- and α-alkoxy-substituted carboxylic acids with extremely high enantioselectivities (ee up to 99.8%) and reactivities (TON up to 10 000) under mild conditions. The hydrogenation of R-benzyloxy-substituted α,β-unsaturated acids provided an efficient alternative for the synthesis of chiral R-hydroxy acids after an easy deprotection. A mechanism involving a catalytic cycle between IrI and IrIII was proposed on the basis of the coordination model of the unsaturated acids with the iridium metal center. The rationality of the catalytic cycle, with an olefin dihydride complex as the key intermediate, was supported by the deuterium-labeling studies. The X-ray diffraction analysis of the single crystal of catalyst revealed that the rigid and sterically hindered chiral environment created by the spiro phosphino-oxazoline ligands is the essential factor that permits the catalyst to obtain excellent chiral discrimination. A chiral induction model was suggested on the basis of the catalyst structure and the product configuration.
- Li, Shen,Zhu, Shou-Fei,Xie, Jian-Hua,Song, Song,Zhang, Can-Ming,Zhou, Qi-Lin
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supporting information; experimental part
p. 1172 - 1179
(2010/04/01)
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- Synthesis of a regular 24-membered cyclodepsipeptide by direct amide cyclization
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Aminoisobutyric Acid, Crystal Structure The synthesis of a 24-membered cyclic depsipeptide with an alternating sequence of phenyllactic acid and α-aminoisobutyric acid (Aib) is described. The linear precursor was prepared via the 'azirine/oxazolone method
- K?ttgen, Peter,Linden, Anthony,Heimgartner, Heinz
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experimental part
p. 689 - 698
(2009/12/26)
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- An inexpensive carbohydrate derivative used as a chiral auxiliary in the synthesis of α-hydroxy carboxylic acids
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Protected α-hydroxy carboxylic acids were synthesized in moderate yield and high diastereoselectivity by alkylation of glycolate (α-hydroxy acetate) enolates using a D-fructose-derived chiral auxiliary. The new chiral center was assigned the R configuration based on comparisons of optical rotations and on one crystal structure analysis. This alkylation methodology is compatible with several hydroxyl protecting groups. The free hydroxy acids were obtained upon removal of the protecting group from the hydroxyl functionality followed by saponification.
- Yu, Hongwu,Ballard, C.Eric,Boyle, Paul D,Wang, Binghe
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p. 7663 - 7679
(2007/10/03)
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- Development of new hydroxamate matrix metalloproteinase inhibitors derived from functionalized 4-aminoprolines
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A series of hydroxamates was prepared from an aminoproline scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for five enzymes within the MMP family, and a number of inhibitors, such as compound 47, display broad-spectrum activity with sub-nanomolar potency for some enzymes. Modifications of the P1′ portion of the molecule played a key role in affecting both potency and selectivity within the MMP family. Longer-chain aliphatic substituents in this region of the molecule tended to increase potency for MMP-3 and decrease potency for MMP-1, as exemplified by compounds 48-50, while aromatic substituents, as in compound 52, generated broad-spectrum inhibition. The data is rationalized based upon X-ray crystal data which is also presented. While the in vitro peroral absorption seemed to be less predictable, it tended to decrease with longer and more hydrophilic substituents. Finally, a rat model of osteoarthritis was used to evaluate the efficacy of these compounds, and a direct link was established between their pharmacokinetics and their in vivo efficacy.
- Natchus,Bookland,De,Almstead,Pikul,Janusz,Heitmeyer,Hookfin,Hsieh,Dowty,Dietsch,Patel,Garver,Gu,Pokross,Mieling,Baker,Foltz,Peng,Bornes,Strojnowski,Taiwo
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p. 4948 - 4963
(2007/10/03)
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- ASYMMETRIC ALKYLATION OF N-ACYLSULTAMS: A GENERAL ROUTE TO ENANTIOMERICALLY PURE, CRYSTALLINE C(α,α)-DISUBSTITUTED CARBOXYLIC ACID DERIVATIVES.
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Successive treatment of acylsultams 2 with nBuLi or NHMDS and primary alkyl halides, followed by crystallization, gave pure C(α)-alkylation products 4 and, via their non-destructive cleavage, enantiomerically pure alcohols 5 or carboxylic acids 6.
- Oppolzer, Wolfgang,Moretti, Robert,Thomi, Silvia
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p. 5603 - 5606
(2007/10/02)
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- A HIGHLY EFFECTIVE ASYMMETRIC SYNTHESIS OF α-HYDROXY ACIDS BY ALKYLATION OF CHIRAL N-(BENZYLOXYACETYL)-TRANS-2,5-BIS(METHOXYMETHOXYMETHYL)PYRROLIDINE
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Alkylation of lithiated N-(benzyloxyacetyl)-trans-2,5-bis(methoxymethoxymethyl)-pyrrolidine proceeded with high stereoselectivity (>96percent de) and subsequent transformations of the alkylated products gave synthetically useful α-benzyloxy acids or α-hydroxy acids of high enantiomeric purity.
- Enomoto, Masayuki,Ito, Yoshio,Katsuki, Tsutomu,Yamaguchi, Masaru
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p. 1343 - 1344
(2007/10/02)
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