53912-80-4Relevant articles and documents
Synthesis of Optically Active N -(4-Hydroxynon-2-enyl)pyrrolidines: Key Building Blocks in the Total Synthesis of Streptomyces coelicolor Butanolide 5 (SCB-5) and Virginiae Butanolide A (VB-A)
Donges, Jonas,Hofmann, Sandra,Walter, Johannes C.,Reichertz, Julia,Brüggemann, Moritz,Frank, Andrea,Nubbemeyer, Udo
supporting information, p. 2632 - 2642 (2021/04/27)
Starting from 5-methylhexanal and (S)-configured N -propargylprolinol ethers, coupling delivered N -(4-hydroxynon-2-ynyl)prolinol derivatives as mixtures of C4 diastereomers. Resolution of the epimers succeeded after introduction of an (R)-mandelic ester derivative and subsequent HPLC separation. Alternatively, suitable oxidation gave the corresponding alkynyl ketone. Midland reagent controlled diastereoselective reduction afforded a defined configured propargyl alcohol with high selectivity. LiAlH 4reduction and Mosher analyses of the allyl alcohols enabled structure elucidation. The suitably protected products are used as key intermediates in enantioselective Streptomyces γ-butyrolactone signaling molecule total syntheses.
Understanding the Alkylation Mechanism of 3-Chloropiperidines – NMR Kinetic Studies and Isolation of Bicyclic Aziridinium Ions
Helbing, Tim,Georg, Mats,St?hr, Fabian,Carraro, Caterina,Becker, Jonathan,Gatto, Barbara,G?ttlich, Richard
, p. 5905 - 5913 (2021/10/29)
The present study describes the kinetic analysis of the 3-chloropiperidine alkylation mechanism. These nitrogen mustard-based compounds are expected to react via a highly electrophilic bicyclic aziridinium ion, which is readily attacked by nucleophiles. Halide abstraction using silver salts with weakly coordinating anions lead to the isolation of these proposed intermediates, whereas their structure was confirmed by single crystal XRD. Kinetic studies of the aziridinium ions also revealed notable reactivity differences of the C5 gem-methylated compounds and their unmethylated counterparts. The observed reactivity trends were also reflected by NMR studies in aqueous solution and DNA alkylation experiments of the related 3-chloropiperidines. Therefore, the underlying Thorpe-Ingold effect might be considered as another option to adjust the alkylation activity of these compounds.
l -Proline as a Valuable Scaffold for the Synthesis of Novel Enantiopure Neonicotinoids Analogs
Bonilla-Landa, Israel,Cuapio-Mu?oz, Ulises,Luna-Hernández, Axel,Reyes-Luna, Alfonso,Rodríguez-Hernández, Alfredo,Ibarra-Juarez, Arturo,Suarez-Mendez, Gabriel,Barrera-Méndez, Felipe,Caram-Salas, Nadia,Enríquez-Medrano, J. Francisco,Díaz De León, Ramón E.,Olivares-Romero, José Luis
, p. 1455 - 1465 (2021/02/16)
In this research, six neonicotinoid analogs derived from l-proline were synthesized, characterized, and evaluated as insecticides against Xyleborus affinis. Most of the target compounds showed good to excellent insecticidal activity. To the best of our knowledge, this is the first report dealing with the use of enantiopure l-proline to get neonicotinoids. These results highlighted the compound 9 as an excellent candidate used as the lead chiral insecticide for future development. Additionally, molecular docking with the receptor and compound 9 was carried out to gain insight into its high activity when compared to dinotefuran. Finally, the neurotoxic evaluation of compound 9 showed lower toxicity than the classic neonicotinoid dinotefuran.
Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides
Ong, Derek Yiren,Yen, Zhihao,Yoshii, Asami,Revillo Imbernon, Julia,Takita, Ryo,Chiba, Shunsuke
supporting information, p. 4992 - 4997 (2019/03/13)
New protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX2). Use of a different halide on ZnX2 dictates the selectivity, wherein the NaH-ZnI2 system delivers alcohols and NaH-ZnCl2 gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH2)∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H?Zn?Cl)2 is the key species for the production of amines.
Synthesis of diastereomeric pyrrolidine sulfamides via anchimerically assisted nucleophilic substitution reactions
Vargas-Caporali, Jorge,van der Lee, Arie,Dewynter, Georges,Juaristi, Eusebio
supporting information, p. 352 - 358 (2018/05/22)
The Mitsunobu reaction was employed in a key step during the development of a convenient synthetic route for the enantioselective preparation of pyrrolidine-sulfamide ligands from (R)- or (S)- [(S)-1-benzylpyrrolidin-2-yl](phenyl)methanol, and employing tert-butyl pyrrolidin-1-yl-sulfonylcarbamate as a non-conventional nucleophilic source. Although it is well documented that the exposure of this type of diastereomeric amino alcohols to the above-mentioned nucleophile usually leads to the formation of piperidines via ring expansion, either through classical nucleophilic substitution or the Mitsunobu version, only the pyrrolidine derivatives were generated with retention of configuration on the exocyclic stereocenter, owing to the neighboring group participation (internal backside nucleophilic substitution, SNib). Final removal of the N-Boc protecting group from the sulfamide fragment afforded chiral compounds with significant potential as chiral ligands in asymmetric catalysis.
Reduction of N,N-Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite
Chan, Guo Hao,Ong, Derek Yiren,Yen, Zhihao,Chiba, Shunsuke
, (2018/05/14)
A new and concise protocol for selective reduction of N,N-dimethylamides into aldehydes was established using sodium hydride (NaH) in the presence of sodium iodide (NaI) under mild reaction conditions. The present protocol with the NaH-NaI composite allows for reduction of not only aromatic and heteroaromatic but also aliphatic N,N-dimethylamides with wide substituent compatibility. Retention of α-chirality in the reduction of α-enantioriched amides was accomplished. Use of sodium deuteride (NaD) offers a new step-economical alternative to prepare deuterated aldehydes with high deuterium incorporation rate. The NaH-NaI composite exhibits unique chemoselectivity for reduction of N,N-dimethylamides over ketones.
Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
van Greunen, Divan G.,Cordier, Werner,Nell, Margo,van der Westhuyzen, Chris,Steenkamp, Vanessa,Panayides, Jenny-Lee,Riley, Darren L.
, p. 671 - 690 (2017/02/10)
A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.
Transition Metal-Free Selective Double sp3 C-H Oxidation of Cyclic Amines to 3-Alkoxyamine Lactams
Osorio-Nieto, Urbano,Chamorro-Arenas, Delfino,Quintero, Leticia,H?pfl, Herbert,Sartillo-Piscil, Fernando
, p. 8625 - 8632 (2016/09/28)
The first chemical method for selective dual sp3 C-H functionalization at the alpha-and beta positions of cyclic amines to their corresponding 3-alkoxyamine lactams is reported. Unlike traditional Cα-H oxidation of amines to amides mediated by transition metals, the present protocol, which involves the use of NaClO2/TEMPO/NaClO in either aqueous or organic solvent, not only allows the Cα-H oxidation but also the subsequent functionalization of the unreactive β-methylene group in an unprecedented tandem fashion and using environmentally friendly reactants.
Resin-immobilized pyrrolidine-based chiral organocatalysts for asymmetric Michael additions of ketones and aldehydes to nitroolefins
Zhang, Richeng,Yin, Guohui,Li, Yang,Yan, Xilong,Chen, Ligong
, p. 3461 - 3464 (2015/02/18)
Based on the electrostatic adsorption between acidic resins and organocatalysts, a series of resin-supported chiral organocatalysts were designed and synthesized. They were evaluated for the asymmetric Michael addition of cyclohexanone with nitrostyrene, in which, catalyst 3 (Fig. 1) exhibited the best catalytic performance. This reaction proceeded under catalyst 3 smoothly at room temperature without any solvent or additive and could give product with high yield (95%) and good stereoselectivity (90% ee, 98:2 dr). Encouragingly, catalyst 3 was easily isolated and reused for 16 consecutive runs without obvious loss of reaction enantioselectivity. Furthermore, it was successfully applied to catalyze the reactions of a series of ketones and aldehydes with nitroolefins.
Flexible synthesis of planar chiral azoninones and optically active indolizidinones
Bohland, Frank,Erlin, Irina,Platte, Lukas,Schr?der, Maike,Schollmeyer, Dieter,Nubbemeyer, Udo
supporting information, p. 6272 - 6284 (2015/03/30)
The flexible synthesis of defined substituted optically active indolizidinones starting from chiral pool (S)-proline and trans 4-hydroxy-(S)-proline is described. Several defined 2-vinylpyrrolidines were generated in short sequences. The aza-Claisen rearr
