4897-55-6Relevant academic research and scientific papers
Zirconium-hydride-catalyzed site-selective hydroboration of amides for the synthesis of amines: Mechanism, scope, and application
Han, Bo,Jiao, Haijun,Wu, Lipeng,Zhang, Jiong
, p. 2059 - 2067 (2021/09/02)
Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective. In this respect, catalytic deoxygenative amide reduction has proven to be promising but challenging, as this approach necessitates selective C–O bond cleavage. Herein, we report the selective hydroboration of primary, secondary, and tertiary amides at room temperature catalyzed by an earth-abundant-metal catalyst, Zr-H, for accessing diverse amines. Various readily reducible functional groups, such as esters, alkynes, and alkenes, were well tolerated. Furthermore, the methodology was extended to the synthesis of bio- and drug-derived amines. Detailed mechanistic studies revealed a reaction pathway entailing aldehyde and amido complex formation via an unusual C–N bond cleavage-reformation process, followed by C–O bond cleavage.
A practical catalytic reductive amination of carboxylic acids
Andrews, Keith G.,Denton, Ross M.,Hirst, David J.,Stoll, Emma L.,Tongue, Thomas,Valette, Damien
, p. 9494 - 9500 (2020/10/02)
We report reductive alkylation reactions of amines using carboxylic acids as nominal electrophiles. The two-step reaction exploits the dual reactivity of phenylsilane and involves a silane-mediated amidation followed by a Zn(OAc)2-catalyzed amide reduction. The reaction is applicable to a wide range of amines and carboxylic acids and has been demonstrated on a large scale (305 mmol of amine). The rate differential between the reduction of tertiary and secondary amide intermediates is exemplified in a convergent synthesis of the antiretroviral medicine maraviroc. Mechanistic studies demonstrate that a residual 0.5 equivalents of carboxylic acid from the amidation step is responsible for the generation of silane reductants with augmented reactivity, which allow secondary amides, previously unreactive in zinc/phenylsilane systems, to be reduced.
Synthesis of tertiary amines by direct Br?nsted acid catalyzed reductive amination
Hussein, Mohanad A.,Dinh, An H.,Huynh, Vien T.,Nguyen, Thanh Vinh
supporting information, p. 8691 - 8694 (2020/08/21)
Tertiary amines are ubiquitous and valuable compounds in synthetic chemistry, with a wide range of applications in organocatalysis, organometallic complexes, biological processes and pharmaceutical chemistry. One of the most frequently used pathways to synthesize tertiary amines is the reductive amination reaction of carbonyl compounds. Despite developments of numerous new reductive amination methods in the past few decades, this reaction generally requires non-atom-economic processes with harsh conditions and toxic transition-metal catalysts. Herein, we report simple yet practical protocols using triflic acid as a catalyst to efficiently promote the direct reductive amination reactions of carbonyl compounds on a broad range of substrates. Applications of this new method to generate valuable heterocyclic frameworks and polyamines are also included.
Visible-Light-Mediated C(sp3)–H Thiocarbonylation for Thiolactam Preparation with Potassium Sulfide
Tan, Wei,Wang, Cuihong,Jiang, Xuefeng
supporting information, p. 1234 - 1238 (2019/11/21)
We report herein a protocol for thiolactam preparation with potassium sulfide via visible-light-mediated C(sp3)–H thiocarbonylation, in which polysulfide dianions and radical anions generated from potassium sulfide were the key active species. A variety of thiolactams were straightforward established under mild conditions. Moreover, it was successfully applied to structural modification of tetrahydroberberine.
Dehydrogenative Aromatization and Sulfonylation of Pyrrolidines: Orthogonal Reactivity in Photoredox Catalysis
Muralirajan, Krishnamoorthy,Kancherla, Rajesh,Rueping, Magnus
supporting information, p. 14787 - 14791 (2018/10/20)
Oxidative dehydrogenative aromatization and selective sulfonylation reactions of N-heterocycles under visible-light photoredox catalysis were established. The mild reaction conditions make this approach an appealing and versatile strategy to functionalize/oxidize pyrrolidines whereby arylsulfonyl chlorides were identified to be both catalyst regeneration and sulfonylation reagents.
Structure-based optimization leads to the discovery of NSC765844, a highly potent, less toxic and orally efficacious dual PI3K/mTOR inhibitor
Han, Jinsong,Chen, Ying,Yang, Chao,Liu, Ting,Wang, Mingping,Xu, Haojie,Zhang, Ling,Zheng, Canhui,Song, Yunlong,Zhu, Ju
, p. 684 - 701 (2016/07/21)
The phosphoinositide 3-kinase (PI3K) family is one of the most frequently activated enzymes in a wide range of human cancers; thus, inhibition of PI3K represents a promising strategy for cancer therapy. Herein, a series of benzylamine substituted arylsulfonamides were designed and synthesized as dual PI3K/mTOR inhibitors using a strategy integrating focused library design and virtual screening, resulting in the discovery of 13b (NSC765844). The compound 13b exhibits highly potent enzyme inhibition with IC50s of 1.3, 1.8, 1.5, 3.8 and 3.8?nM for PI3Kα, β, γ, δ, and mTOR, respectively. 13b was further evaluated in NCI by an in?vitro cytotoxic screening program. Broad-spectrum antitumor activities with mean GI50value of 18.6?nM against approximately 60 human tumor cell lines were found. 13b displayed favorable physicochemical properties and superior pharmacokinetic profiles for animal studies. It significantly inhibited tumor growth when administered orally in an A549 non-small-cell lung carcinoma xenograft and BEL7404 human hepatocellular carcinoma xenograft models. On the basis of its excellent in?vivo efficacy and superior pharmacokinetic profiles, 13b has been selected for further preclinical investigation as a promising anticancer drug candidate.
Novel Potent Proline-Based Metalloproteinase Inhibitors: Design, (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron Emission Tomography
Kalinin, Dmitrii V.,Wagner, Stefan,Riemann, Burkhard,Hermann, Sven,Schmidt, Frederike,Becker-Pauly, Christoph,Rose-John, Stefan,Sch?fers, Michael,Holl, Ralph
supporting information, p. 9541 - 9559 (2016/11/11)
As dysregulation of matrix metalloproteinase (MMP) activity is associated with a wide range of pathophysiological processes like cancer, atherosclerosis, and arthritis, MMPs represent a valuable target for the development of new therapeutics and diagnostic tools. We herein present the chiral pool syntheses, in vitro evaluation, and SAR studies of a series of d- and l-proline- as well as of (4R)-4-hydroxy-l-proline-derived MMP inhibitors possessing general formula 1. Some of the synthesized hydroxamic acids were found to be potent MMP inhibitors with IC50 values in the nanomolar range, also demonstrating no off-target effects toward the other tested Zn2+-dependent metalloproteases (ADAMs and meprins). Utilizing the structure of the (2S,4S)-configured 4-hydroxyproline derivative 4, a selective picomolar inhibitor of MMP-13, the radiolabeled counterpart [18F]4 was successfully synthesized. The radiotracer's biodistribution in mice as well as its serum stability were evaluated for assessing its potential use as a MMP-13 targeting PET imaging agent.
Interfacial hydrogenation and deamination of nitriles to selectively synthesize tertiary amines
Lu, Shuanglong,Li, Chao,Wang, Jiaqing,Pan, Yue,Cao, Xueqing,Gu, Hongwei
supporting information, p. 11110 - 11113 (2014/10/15)
A novel one-pot method has been developed for the interfacial hydrogenation of nitriles to synthesize asymmetrical tertiary amines. The active Pt NWs allow for the preparation of a series of tertiary amines in excellent yields (up to 99.0%) and a mixed solvent is vital for the adjustment of the yield. And also, the reaction proceeded under mild conditions and is environmentally friendly.
Iridium-catalyzed decarboxylative N-alkylation of α-amino acids with primary alcohols
Wu, Jiashou,Jiang, Huajiang,Chen, Dingben,Shen, Jianfen,Zhao, Datong,Xiang, Jing,Zhou, Qizhong
, p. 539 - 542 (2014/03/21)
A new decarboxylative N-alkylation reaction of α-amino acids has been developed. A variety of tertiary amines were obtained in good to excellent yields via the decarboxylative N-alkylation reaction of α-amino acids with primary alcohols catalyzed by a CpIr complex. Georg Thieme Verlag Stuttgart New York.
The structure-activity relationships of L3MBTL3 inhibitors: Flexibility of the dimer interface
Camerino, Michelle A.,Zhong, Nan,Dong, Aiping,Dickson, Bradley M.,James, Lindsey I.,Baughman, Brandi M.,Norris, Jacqueline L.,Kireev, Dmitri B.,Janzen, William P.,Arrowsmith, Cheryl H.,Frye, Stephen V.
supporting information, p. 1501 - 1507 (2013/11/19)
We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding.
