64920-29-2Relevant academic research and scientific papers
Visible-Light-Mediated Carbonyl Alkylative Amination to All-Alkyl α-Tertiary Amino Acid Derivatives
Blackwell, J. Henry,Kumar, Roopender,Gaunt, Matthew J.
, p. 1598 - 1609 (2021)
The all-alkyl α-tertiary amino acid scaffold represents an important structural feature in many biologically and pharmaceutically relevant molecules. Syntheses of this class of molecule, however, often involve multiple steps and require activating auxiliary groups on the nitrogen atom or tailored building blocks. Here, we report a straightforward, single-step, and modular methodology for the synthesis of all-alkyl α-tertiary amino esters. This new strategy uses visible light and a silane reductant to bring about a carbonyl alkylative amination reaction that combines a wide range of primary amines, α-ketoesters, and alkyl iodides to form functionally diverse all-alkyl α-tertiary amino esters. Br?nsted acid-mediated in situ condensation of primary amine and α-ketoester delivers the corresponding ketiminium species, which undergoes rapid 1,2-addition of an alkyl radical (generated from an alkyl iodide by the action of visible light and silane reductant) to form an aminium radical cation. Upon a polarity-matched and irreversible hydrogen atom transfer from electron rich silane, the electrophilic aminium radical cation is converted to an all-alkyl α-tertiary amino ester product. The benign nature of this process allows for broad scope in all three components and generates structurally and functionally diverse suite of α-tertiary amino esters that will likely have widespread use in academic and industrial settings.
Enantioselective Synthesis of d- and l-α-Amino Acids by Enzymatic Transamination Using Glutamine as Smart Amine Donor
Heuson, Egon,Charmantray, Franck,Petit, Jean-Louis,de Berardinis, Véronique,Gefflaut, Thierry
supporting information, p. 778 - 785 (2019/01/04)
Enzymatic transamination is a useful method for the green and highly enantioselective synthesis of chiral amines and non-canonical amino acids which are of major importance as intermediates in medicinal chemistry. However, transamination reactions are usually reversible and synthetic applications of transaminases often require the implementation of an equilibrium shift strategy. Herein, we report a highly effective approach using glutamine as smart amine donor. This amino acid is converted upon transamination into 2-oxoglutaramate which undergoes a fast cyclisation displacing the transamination equilibrium. We have developed a new activity assay in order to identify transaminases from biodiversity able to convert various α-keto acids into valuable amino acids of l- or d-series in the presence of glutamine as amine donor. Discovered transaminases were then used to prepare in high yield and with high enantioselectivity three amino acids of pharmaceutical importance, homophenylalanine, homoalanine and tert-leucine by simply using a nearly stoichiometric amount of glutamine as amine donor. (Figure presented.).
Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors
Burkett, Daniel J.,Wyatt, Brittney N.,Mews, Mallory,Bautista, Anson,Engel, Ryan,Dockendorff, Chris,Donaldson, William A.,St. Maurice, Martin
, p. 4041 - 4047 (2019/08/26)
Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC50 values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.
Enantioselective Organocatalyzed Consecutive Synthesis of Alkyl 4,5-Dihydrofuran-2-carboxylates from α-Keto Esters and (Z)-β-Chloro-β-nitrostyrenes
Becerra, Diana,Raimondi, Wilfried,Dauzonne, Daniel,Constantieux, Thierry,Bonne, Damien,Rodriguez, Jean
supporting information, p. 195 - 201 (2016/12/24)
Alkyl 4,5-dihydrofuran-2-carboxylates can be efficiently obtained via an enantioselective organocatalyzed consecutive reaction between α-keto esters and (Z)-(2-chloro-2-nitroethenyl)benzenes. The overall sequence combines a (R,R)-TUC-catalyzed Michael addition with a DABCO-promoted intramolecular O-alkylation leading to the title products as single diastereomers with enantiomeric excesses from 86% up to 97%.
Novel Synthesis of α-Keto Esters and Amides by an sp3 C-H Oxidation of Nitromethyl Aryl Ketones Promoted by Ion-Supported (Diacetoxyiodo)benzene
Jiang, Xiaoying,Gan, Bing,Liu, Jiwei,Xie, Yuanyuan
supporting information, p. 2737 - 2741 (2016/11/25)
A simple and efficient method is described for the preparation of α-keto esters or amides from nitromethyl aryl ketones. In the presence of nucleophiles (alcohols or amines), the ion-supported (di-acetoxyiodo)benzene-promoted sp3 C-H oxidation of nitromethyl aryl ketones proceeded efficiently under mild conditions to give the corresponding α-keto esters and amides in moderate to good yields. This is the first reported use of (diacetoxyiodo)benzene in the synthesis of α-keto esters and amides. The reaction is ecofriendly and has the -advantages of mild conditions, short reaction times, and a recyclable reagent.
Catalytic cyclization reactions of Huisgen zwitterion with -ketoesters by in situ chemoselective phosphine oxide reduction
Fourmy, Kévin,Voituriez, Arnaud
supporting information, p. 1537 - 1540 (2015/03/30)
The first examples of catalytic cyclization reactions between the Huisgen zwitterion and α-ketoester derivatives are reported. The use of phenylsilane with a substoichiometric amount of bis(p-nitrophenyl)phosphate/diisopropylethylamine proved to be crucial for the in situ reduction of the phosphine oxide formed during the reaction. The optimized protocol is applied to alkyl or aryl ketoesters, furnishing either the corresponding cycloadducts or the hydrazone derivatives, depending on the substitution patterns of the substrates, in moderate to good yields (up to 80% yield, 18 examples).
A novel method for synthesis of α-keto esters with phenyliodine(III) diacetate
Xie, Yuanyuan,Liu, Jiwei,Huang, Yingyi,Yao, Lixia
supporting information, p. 3793 - 3795 (2015/06/08)
A rapid and efficient synthesis of α-keto esters from β-ketonitriles using phenyliodine(III) diacetate is reported. This protocol gave α-keto esters in good yields. This is the first time to report the application of hypervalent iodine(III) reagents in the synthesis of α-keto esters. A plausible reaction mechanism is proposed.
Simplified procedure for TEMPO-catalyzed oxidation: Selective oxidation of alcohols, α-hydroxy esters, and amides using TEMPO and calcium hypochlorite
Reddy, Sabbasani Rajasekhara,Stella, Selvaraj,Chadha, Anju
experimental part, p. 3493 - 3503 (2012/09/22)
A wide range of primary and secondary multifunctional alcohols, α-hydroxyamides, and α-hydroxyesters were oxidized to their corresponding aldehydes, ketones, α-ketoamides, and α-ketoesters under mild reaction conditions using 2,2,6,6-tetramethylpiperidine-1-oxyl as a catalyst with calcium hypochlorite as an oxidant [TEMPO-Ca(OCl)2]. This simplified method does not require any transition metals, acids, or bases and demonstrates controlled and selective oxidation of structurally diverse alcohols, affording moderate to excellent yields at room temperature.
Catalytic enantioselective protonation of α-oxygenated ester enolates prepared through phospha-brook rearrangement
Hayashi, Masashi,Nakamura, Shuichi
supporting information; experimental part, p. 2249 - 2252 (2011/04/16)
(Chemical Equation Presented) Phosphonates go chiral: The organocatalytic enantioselective reaction of α-ketoesters with phosphites using cinchona alkaloids and Na2CO3 has afforded α-phosphonyloxy esters with high enantioselectivities (see scheme). This process allows the formation of both enantiomers of the product. A catalyst loading of as low as 2 mol% does not result in a significant decrease of the enantioselectivity.
Highly enantioselective hydrogenation of 2-oxo-4-arybutanoic acids to 2-hydroxy-4-arylbutanoic acids
Zhu, Lufeng,Chen, Houhe,Meng, Qinghua,Fan, Weizheng,Xie, Xiaomin,Zhang, Zhaoguo
supporting information; experimental part, p. 6186 - 6190 (2011/09/19)
The Ru-catalyzed asymmetric hydrogenation of 2-oxo-4-arybutanoic acids to afford 2-hydroxy-4-arybutanoic acids was accomplished by employing SunPhos as chiral ligand and 1 M aq HBr as additive. The high enantioselectivities (88.4%-92.6% ee) and efficiency (TON=10,000, TOF=300 h-1) make this method efficient for the synthesis of an important intermediate, (R)-2-hydroxy-4-phenylbutanoic acid, for ACE inhibitors.
