66399-75-5Relevant academic research and scientific papers
Continuous flow heterogeneous catalytic reductive aminations under aqueous micellar conditions enabled by an oscillatory plug flow reactor
?tv?s, Sándor B.,Buchholcz, Balázs,Darvas, Ferenc,Kappe, C. Oliver,Novák, Zoltán,Sipos, Gellért,Wernik, Michaela
, p. 5625 - 5632 (2021/08/16)
Despite the fact that continuous flow processing exhibits well-established technical advances, aqueous micellar chemistry, a field that has proven extremely useful in shifting organic synthesis to sustainable water-based media, has mostly been explored under conventional batch-based conditions. This is particularly because of the fact that the reliable handling of slurries and suspensions in flow has been considered as a significant technical challenge. Herein, we demonstrate that the strategic application of an oscillatory plug flow reactor enables heterogeneous catalytic reductive aminations in aqueous micellar media enhancing mass transport and facilitating process simplicity, stability and scalability. The micellar flow process enabled a broad range of substrates, including amino acid derivatives, to be successfully transformed under reasonably mild conditions utilizing only very low amounts of Pd/C as a readily available heterogeneous catalyst. The preparative capabilities of the process along with the recyclability of the heterogenous catalyst and the aqueous reaction media were also demonstrated. This journal is
Benzoazepine-Fused Isoindolines via Intramolecular (3 + 2)-Cycloadditions of Azomethine Ylides with Dinitroarenes
Wales, Steven M.,Rivinoja, Daniel J.,Gardiner, Michael G.,Bird, Melissa J.,Meyer, Adam G.,Ryan, John H.,Hyland, Christopher J. T.
supporting information, p. 4703 - 4708 (2019/06/27)
Aminobenzaldehydes bearing a pendant 3,5-dinitrophenyl group react thermally with N-substituted α-amino acids to form unprecedented benzoazepine-fused isoindolines. The reaction proceeds via a dearomatization/rearomatization sequence involving an intramolecular (3 + 2)-cycloaddition between the in situ formed azomethine ylide and the dinitroarene. Various glycine derivatives are tolerated as well as branched substrates based on cyclic, α-mono-, and α,α-disubstituted amino acids, giving single diastereomers in many cases. The method is scalable and gives products with a nitro group ready for further manipulation.
Memory of Chirality Concept in Asymmetric Intermolecular Michael Addition of α-Amino Ester Enolates to Enones and Nitroalkenes
Veeraswamy, Vadlamuri,Goswami, Gaurav,Mukherjee, Satobhisha,Ghosh, Koena,Saha, Manik Lal,Sengupta, Arunava,Ghorai, Manas K.
, p. 1106 - 1115 (2018/02/09)
A highly stereoselective asymmetric intermolecular conjugate addition of α-amino ester derivatives to cyclic enones via the memory of chirality (MOC) concept in high yields with excellent diastereo- and enantioselectivity (dr >99:1, up to 99% ee) is reported. The applicability and the generality of the strategy was demonstrated by its further exploration to acyclic α,β-unsaturated ketone and aromatic nitroalkenes, resulting in the formation of δ-keto-α-amino ester derivative and γ-nitro-α-amino ester derivatives, respectively, with excellent ee and dr.
Chiral-pool synthesis of 1,2,4-trisubstituted 1,4-diazepanes as novel σ1 receptor ligands
Fanter, Lena,Müller, Christoph,Schepmann, Dirk,Bracher, Franz,Wünsch, Bernhard
, p. 4778 - 4799 (2017/10/05)
Starting from enantiomerically pure amino acids, 1,4-diazepanes with various substituents in 1, 2, and 4-position were synthesized following the late stage diversification strategy. The key step in the formation of the seven-membered ring was the intramolecular EDC coupling of amino acids 15, 26, and 39. The configuration in 2-position does not influence the σ1 affinity and selectivity over related receptors. A cyclohexylmethyl or a butyl group are the preferred substituents in 4-position, whereas a methyl moiety in 2-position and a (substituted) benzyl moiety in 1-position result in the highest σ1 affinity. These results fit nicely to the reported σ1 pharmacophore models. The compounds did not inhibit the structurally related fungal enzyme sterol Δ8,7-isomerase, but showed inhibition of diverse enzymes in late cholesterol biosynthesis at high concentrations. In a screening against more than 50 target proteins, (2S)-1-benzyl-4-(4-methoxybenzyl)-2-methyl-1,4-diazepane ((S)-28b, Ki(σ1) = 0.86 nM) showed a clean receptor profile. The dose dependent potentiation of electrically stimulated contractions of guinea pig vas deferens indicates σ1 agonistic activity of (S)-28b. Even at a dose of 100 mg/kg (S)-28b did not induce severe toxic or behavioral effects in the Irwin screen. Clear cognition enhancing effects were observed for (S)-28b after inducing amnesia by scopolamine.
Preparation of the optically pure N-methyl amino ester method and product
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Paragraph 0053-0054, (2017/04/13)
The invention belongs to the field of organic synthesis of amino acids and discloses a method for preparing optically pure N-methyl amino-acid ester. The method comprises the following steps of carrying out esterification reaction on amino acid as a starting raw material and aldehyde to form an imine intermediate, carrying out reductive amination in the presence of palladium carbon, and carrying out hydrogenation and debenzylation to finally synthesize optically pure N-methyl amino-acid ester. The method has the advantages of simplicity in method, mild reaction conditions and good adaptability and side chains of D-type or L-type amino acid do not need to be protected.
Broadening the chemical scope of laccases: Selective deprotection of N-benzyl groups
Martínez-Montero, Lía,Díaz-Rodríguez, Alba,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
supporting information, p. 2794 - 2798 (2015/05/27)
Laccase from Trametes versicolor together with TEMPO has been found to be a very efficient system to deprotect N-benzylated primary amines, differing from previously described methods since it uses oxygen as a mild oxidant in aqueous medium. Chemoselective removal of the benzyl group was achieved with excellent yields when secondary amines and alcohol moieties were also present.
Synthesis of enantiomerically enriched indolines and tetrahydroisoquinolines from (S)-amino acid-derived chiral carbocations: An easy access to (3S,4R)-demethoxy-3-isopropyl diclofensine
Manna, Sudipta Kumar,Panda, Gautam
, p. 8318 - 8324 (2015/01/09)
Enantiomerically enriched indolines and tetrahydroisoquinolines were synthesized within 5 min to 2 h in high yields from easily accessible (S)-amino acid derived chiral carbocations. The diastereoselective Friedel-Crafts reaction is promoted by a Lewis acid (AlCl3) offering trans-diastereoselectivity. The rate of the reaction and diastereoselectivity of the product are significantly influenced by steric hindrance of the amino acids substituents and aryl groups. The methodology can be applied for the synthesis of the enantiomerically enriched bioactive scaffold (3S,4R)-demethoxy-3-isopropyl diclofensine. This journal is
Diastereoselective synthesis of novel aza-diketopiperazines via a domino cyclohydrocarbonylation/addition process
Regenass, Pierre,Margathe, Jean-Fran?ois,Mann, André,Suffert, Jean,Hibert, Marcel,Girard, Nicolas,Bonnet, Dominique
supporting information, p. 9657 - 9660 (2014/08/18)
Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(i)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry. This journal is the Partner Organisations 2014.
Diastereoselective intramolecular allyl transfer from allyl carbamate accompanied by 5-endo-trig ring closure
Karjalainen, Oskari K.,Nieger, Martin,Koskinen, Ari M. P.
supporting information, p. 2551 - 2554 (2013/04/10)
To All(oc) involved: A palladium-catalyzed formal 5-endo-trig heteroannulation of enones generated in situ from amino acid derived β-keto nitriles has been realized (see scheme; Alloc=allyl carbamate). The reaction proceeds with allyl-group transfer from the carbamate protecting group to generate two new contiguous stereocenters, including one quaternary center, with high selectivity. Copyright
Combinatorial aid for underprivileged scaffolds: Solution and solid-phase strategies for a rapid and efficient access to novel aza-diketopiperazines (aza-DKP)
Bonnet, Dominique,Margathe, Jean-Francois,Radford, Sally,Pflimlin, Elsa,Riche, Stephanie,Doman, Pete,Hibert, Marcel,Ganesan
, p. 323 - 334 (2012/07/13)
An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4- triazine-3,6-diones has been synthesized starting from Fmoc-l-Pro-OH and various Fmoc-l-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and 1H NMR spectroscopy.
