Functionalized Pyrrolidine Derivatives Research Articles

Synthesis of Highly Functionalized Pyrrolidine Derivatives from Easily Accessible Diethyl (E)‐4‐Oxohex‐2‐enedioate

The diastereoselective synthesis of highly substituted pyrrolidines has been accomplished using a six‐carbon building block bearing carbon atoms with different reactivities. In this reaction, the building block acts a 1,3‐dipole and undergoes cyclization with imines formed in situ to give pyrrolidine derivatives.

Hydroxy-Assisted Regio- and Stereoselective Synthesis of Functionalized 4-Methylenepyrrolidine Derivatives via Phosphine-Catalyzed [3 + 2] Cycloaddition of Allenoates with o-Hydroxyaryl Azomethine Ylides.

In this work, we present a new strategy for the chemo-, regio-, and stereoselective synthesis of functionalized pyrrolidine derivatives via a hydroxy-assisted phosphine-catalyzed reaction of allenoates or substituted allenoates with o-hydroxyaryl azomethine ylides that offers a wide variety of 4-methylenepyrrolidine derivatives in synthetically useful yields with high stereoselctivities under mild conditions. Remarkably, it is the first example of highly regio- and stereoselective phosphine-catalyzed [3 + 2] cycloaddition of allenoates with o-hydroxyaryl azomethine ylides.

Copper(i)-catalyzed 5-exo-trig radical cyclization/borylation of alkyl halides: access to functionalized pyrrolidine derivatives

This work reports the copper(i)-catalyzed 5-exo-trig radical cyclization/borylation of alkyl halides bearing an alkene moiety, during which a C-C bond and a C-B bond were formed in one step. Various functionalized pyrrolidine derivatives bearing a quaternary carbon center were obtained, and they showed good functional group tolerance and high chemoselectivity. This transformation was highly efficient and could be finished in 20 minutes. A radical mechanism has been proposed.

Asymmetric synthesis of functionalized trifluoromethyl-substituted pyrrolidines via an organocatalytic domino Michael/Mannich [3+2] cycloaddition.

The asymmetric synthesis of highly functionalized pyrrolidine derivatives with three contiguous stereogenic centers and bearing a trifluoromethyl group has been developed through an organocatalytic domino Michael/Mannich [3+2] cycloaddition sequence. Employing a commercially available secondary amine as the catalyst, the scalable one-pot protocol occurs with high yields and excellent stereoselectivities, providing a short entry into a series of trifluoromethylated pyrrolidines with potential medical value.

ChemInform Abstract: Proline‐Catalyzed Sequential syn‐Mannich and [4 + 1]‐Annulation Cascade Reactions to Form Densely Functionalized Pyrrolidines.

A highly efficient one-pot [4 + 1]-annulation process for the asymmetric synthesis of densely functionalized pyrrolidine derivatives is described. The in situ generated syn-Mannich adduct obtained via proline catalysis acts as a four-atom component, and Corey’s sulfur ylide or ethyl bromoacetate acts as a one-atom carbon source to construct pyrrolidine units in a highly enantio- and diastereoselective manner.

Proline-catalyzed sequential syn-Mannich and [4 + 1]-annulation cascade reactions to form densely functionalized pyrrolidines.

A highly efficient one-pot [4 + 1]-annulation process for the asymmetric synthesis of densely functionalized pyrrolidine derivatives is described. The in situ generated syn-Mannich adduct obtained via proline catalysis acts as a four-atom component, and Corey's sulfur ylide or ethyl bromoacetate acts as a one-atom carbon source to construct pyrrolidine units in a highly enantio- and diastereoselective manner.

ChemInform Abstract: Synthesis of Glutamic Acid and Highly Functionalized Pyrrolidine Derivatives by Utilizing Tunable Calcium Catalysts for Chemoselective Asymmetric 1,4‐Addition and [3 + 2] Cycloaddition Reactions.

AbstractThe direction of calcium‐catalyzed reaction of Schiff bases with acrylic acid esters and amides depends on the structure of starting compounds leading to either glutamic acid derivatives or substituted pyrrolidines.

Synthesis of Glutamic Acid and Highly Functionalized Pyrrolidine Derivatives by Utilizing Tunable Calcium Catalysts for Chemoselective Asymmetric 1,4‐Addition and [3+2] Cycloaddition Reactions

AbstractA current trend in organic chemistry is the development of highly efficient, environmentally friendly and inexpensive catalysts for asymmetric transformations. Alkaline earth metals, due to their specific chemical properties and abundance in nature, provide promising and challenging catalysts in organic synthesis. This article describes the utilization of alkaline earth metals in the development of an effective catalytic system based on calcium salts in combination with Box‐type ligands. We disclose asymmetric 1,4‐addition and [3+2] cycloaddition reactions using simple catalytic systems consisting of calcium chloride dihydrate, chiral ligands and tetramethylguanidine. Various Box ligands were synthesized and the most effective proved to be that bearing an indane chiral backbone and a cyano group. Depending on the structure of both glycine Schiff bases and α,β‐unsaturated compounds, the corresponding Michael adducts or pyrrolidine derivatives were obtained in moderate to high yields with high enantioselectivities. Modification of the catalytic system by using more Lewis acidic calcium salts such as calcium triflate and neutral Pybox‐type ligands allows a tuning of the chemoselectivity and leads to suppression of the [3+2] cycloadition reactions. Various β‐substituted acrylates provided 1,4‐addition adducts exclusively in high yields with moderate to high diastereo‐ and enantioselectivities. This methodology has broadened a synthetic route to β‐branched glutamic acid derivatives and established calcium salts as useful and attractive catalysts for asymmetric catalysis.

Virtual screening and QSAR study of some pyrrolidine derivatives as α-mannosidase inhibitors for binding feature analysis

Virtual screening and QSAR analysis were carried out to investigate the binding features of (2R, 3R, 4S)-2-aminomethylpyrrolidine 3,4-diol and the functionalized pyrrolidine derivatives to the α-mannosidase I and II enzymes. The QSAR models (possessed considerable R2, Q2 values, etc.) suggested that the presence of polar property on the vdW surface (vsurf_W, vsurf_Wp, etc.) of the molecules is important along with the presence of aromatic rings (opr_violation) in the molecules (which also provide hydrophobicity to the molecules). The docking study performed on α-mannosidase I and II enzymes pointed that the main interactions occur by hydrogen bonds, hydrophobic π–π stacking contacts and salt bridges with the cation calcium (for α-mannosidase I) and close interaction with zinc ion (α-mannosidase II), respectively. The bond flexibility orientates the aromatic ring in the molecules toward the hydrophobic cavity for π–π stacking contacts with the aromatic amino acids (Phe528, Phe329 and Phe659 for α-mannosidase I and Trp95, Tyr269, Phe312, Tyr102 for α-mannosidase II). The pharmacophore analysis also supports the results derived from the docking and QSAR studies. Our results suggest that the best compound to inhibit both classes of α-mannosidase is the compound 30, which may be used to design similar and better inhibitors to next generation drugs.

Cu-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides with β-Phenylsulfonyl Enones. Ligand Controlled Diastereoselectivity Reversal

A catalytic asymmetric procedure for the 1,3-dipolar cycloaddition of (E)-beta-phenylsulfonyl enones with azomethine ylides to provide highly functionalized pyrrolidine derivatives is described. In the presence of chiral Cu(I)-Segphos catalysts the adducts were obtained with high regio-, diastereo-, and enantioselectivity. Interestingly, a switch from endo to exo selectivity was observed when Segphos or DTBM-Segphos ligand was used.

New asymmetric strategy for the total synthesis of naturally occurring (+)-alexine and (−)-7-epi-alexine

A novel and highly convenient process is described for the asymmetric synthesis of polyhydroxylated pyrrolizidine alkaloids, (+)-alexine [(1R,2R,3R,7S,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine] and (−)-7-epi-alexine [(1R,2R,3R,7R,7aS)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine], as the potent glycosidase inhibitors by featuring the efficient and stereodefined elaboration of the functionalized pyrrolidine derivatives, which were, in turn, prepared via stereoselective manipulation of the homochiral allyl alcohol precursors derived from l-xylose.

Organocatalytic Asymmetric Multicomponent [C+NC+CC] Synthesis of Highly Functionalized Pyrrolidine Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Organocatalytic asymmetric multi-component [C+NC+CC] synthesis of highly functionalized pyrrolidine derivatives

The highly chemo- and enantioselective organocatalytic [C+NC+CC] coupling process between aldehydes, dialkyl 2-aminomalonates and α,β-unsaturated aldehydes is presented. The reaction gives access to highly functionalized pyrrolidine derivatives in good yields with >10:1 dr and 90–98% ee.

ChemInform Abstract: Intramolecular Cyclizations of Imines Bearing the 2‐(Thiomethyl)‐3‐trimethylsilyl‐1‐propenyl Terminator. An Efficient New Procedure for the Stereocontrolled Synthesis of Functionalized Pyrrolidine Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Intramolecular cyclizations of imines bearing the 2-(thiomethyl)-3-trimethylsilyl-1-propenyl terminator. An efficient new procedure for the stereocontrolled synthesis of functionalized pyrrolidine derivatives.

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTIntramolecular Cyclizations of Imines Bearing the 2-(Thiomethyl)-3-trimethylsilyl-1-propenyl Terminator. An Efficient New Procedure for the Stereocontrolled Synthesis of Functionalized Pyrrolidine DerivativesDavid Duncan and Tom LivinghouseView Author Information Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717 [email protected]Cite this: J. Org. Chem. 2001, 66, 15, 5237–5240Publication Date (Web):July 4, 2001Publication History Received30 October 2000Published online4 July 2001Published inissue 1 July 2001https://doi.org/10.1021/jo0015366Copyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views454Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (68 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Cyclization,Molecular structure,Pyrrolidines,Reaction products,Stereoselectivity Get e-Alerts