- Enantioselective dearomative [3+2] annulation of 5-amino-isoxazoles with quinone monoimines
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The first enantioselective dearomative [3+2] annulation of 5-amino-isoxazoles with quinone monoimines was realized using a chiral phosphoric acid as catalyst. Various novel (bridged) isoxazoline fused dihydrobenzofurans bearing two continuous quaternary stereocenters were achieved in moderate to good yields (up to 94%) with moderate to good enantioselectivities (up to 98% ee). The absolute configurations of two products were assigned by X-ray crystal structural analyses and a plausible reaction mechanism was proposed. This journal is
- Liu, Hui,Yan, Yingkun,Zhang, Jiayan,Liu, Min,Cheng, Shaobing,Wang, Zhouyu,Zhang, Xiaomei
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supporting information
p. 13591 - 13594
(2020/11/17)
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- Reactions of 5-Aminoisoxazoles with α-Diazocarbonyl Compounds: Wolff Rearrangement vs N-H Insertion
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A highly chemoselective reaction between 5-aminoisoxazoles and α-diazocarbonyl compounds has been described. Both Wolff rearrangement and N-H insertion products can be obtained selectively by the judicious choice of reaction conditions. In the case of the
- Ge, Yun,Sun, Wangbin,Chen, Yang,Huang, Yulin,Liu, Zhuang,Jiang, Yaojia,Loh, Teck-Peng
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p. 2676 - 2688
(2019/02/26)
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- Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity
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Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.
- De Vita, Elena,Schüler, Peter,Lovell, Scott,Lohbeck, Jasmin,Kullmann, Sven,Rabinovich, Eitan,Sananes, Amiram,He?ling, Bernd,Hamon, Veronique,Papo, Niv,Hess, Jochen,Tate, Edward W.,Gunkel, Nikolas,Miller, Aubry K.
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supporting information
p. 8859 - 8874
(2018/10/09)
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- Hoveyda-Grubbs II Catalyst: A Useful Catalyst for One-Pot Visible-Light-Promoted Ring Contraction and Olefin Metathesis Reactions
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A one-pot reaction to synthesize functionalized 2H-azirines through visible-light-mediated ring contraction and olefin metathesis of isoxazoles is described. Hoveyda-Grubbs II catalyst was found to function as a photocatalyst for these transformations, al
- Ge, Yun,Sun, Wangbin,Pei, Bingbing,Ding, Jia,Jiang, Yaojia,Loh, Teck-Peng
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supporting information
p. 2774 - 2777
(2018/05/22)
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- A convenient synthesis of 4-alkyl-5-aminoisoxazoles
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A series of 4-alkyl-5-aminoisoxazoles have been synthesized in high yield by nucleophilic addition of lithiated alkyl nitriles to (α)-chlorooximes. The scope and limitations of this reaction were examined by varying the nature of the nitrile and chloride
- Bourbeau, Matthew P.,Rider, James T.
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p. 3679 - 3680
(2007/10/03)
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