Search

The review summarizes the methods of synthesis of pyrrolizidine (hexahydro-1H-pyrrolizine) derivatives published in the literature over the past five years. The methods can be conditionally divided into two major groups: synthesis from pyrrolidine derivatives and cyclization of acyclic precursors. [ABSTRACT FROM AUTHOR]

We provide a generalized overview of stereoselective synthetic strategies used for the preparation of tetrahydropyrimidin-2(1H)-one derivatives, illustrated by the most relevant examples published between years 2012 and 2022. The known methods can be divided into two main groups: intramolecular and intermolecular cyclization of unsaturated acyclic amides/ureas, as well as syntheses on the basis of cyclic precursors. [ABSTRACT FROM AUTHOR]

Herein we report a diastereoselective method for the synthesis of bis(pyrrolidine‐1‐carboxamides) via the acid‐catalyzed reaction of 1‐(4,4‐diethoxybutyl)‐3‐arylureas with resorcinol and its derivatives. The proposed method is operationally simple, does not require metal catalysts or chiral promoters and provides target compounds with high diastereoselectivity. [ABSTRACT FROM AUTHOR]

This review summarizes the advances in the synthesis of norhygrine and its derivatives over the past ten years, with special attention paid to stereoselective methods of their preparation. Information on the biological activity of some derivatives of 1‐(pyrrolidin‐2‐yl)propan‐2‐one is presented and the possibility of using pyrrolidines containing a terminal carbonyl group in the synthesis of various alkaloids with useful properties is shown. [ABSTRACT FROM AUTHOR]

Imidazolidin-2-one and 1,3-benzodiazepin-2-one scaffolds are structural motifs of many biologically active compounds. Herein, we report a highly regioselective acid-catalyzed intramolecular nucleophilic cyclization/intermolecular electrophilic substitution reaction sequence of (2,2-dialkoxyethyl)ureas. The reaction benefits from readily available starting materials, a simple workup procedure, moderate to high yields of target compounds, and provides a convenient entry to previously unknown 4-(het)arylimidazolidinones and 5-(het)arylbenzodiazepinones. The proposed mechanism of the reaction is also discussed. [ABSTRACT FROM AUTHOR]

A first successful synthesis of 2‐(het)aryl‐N‐phosphorylpyrrolidines is reported starting from readily available N‐(4,4‐diethoxybutyl)amides of P(V) acids. A range of phenols and hydroxyl‐substituted O‐heterocycles may be employed into the reaction furnishing N‐phosphorylated 2‐(het)arylpyrrolidines with up to 90 % yield. The developed method permits a presence of sensitive to phosphorylation hydroxy groups and provides the easy and regioselective entry to target compounds. [ABSTRACT FROM AUTHOR]

Organophosphorus pyrrolidine derivatives possessing P–N bonds are a promising yet underexplored class of compounds. In this short review we overview the general approaches to these compounds described so far, with a special emphasis on their asymmetric synthesis. 1 Introduction 2 Synthesis of Pyrrolidine-Based P(III) Derivatives 3 Synthesis of Pyrrolidine-Based P(V) Derivatives 3.1 Phosphorylation of Pyrrolidines with P(V) Acid Chlorides 3.2 Phosphorylation of Pyrrolidines with P(V) Acid Esters 3.3 Syntheses via the Atherton–Todd Reaction 3.4 Oxidation of Pyrrolidine-Based P(III) Derivatives 4 Syntheses of N -Phosphorylpyrrolidines from Acyclic Precursors 5 Conclusions [ABSTRACT FROM AUTHOR]

An approach to the synthesis of novel macrocyclic and heterocyclic taurine derivatives based on the reaction of sodium 2-[(4,4-diethoxybutyl)amino]ethanesulfonate with phenols in the presence of trifluoroacetic acid has been developed. The structures of the obtained products are confirmed by spectral data. [ABSTRACT FROM AUTHOR]

Ureas containing alkyl aromatic fragments are an important class of organic compounds due to their high pharmacological activity. However, at the moment there is no common and simple method for the synthesis of these classes of compounds. Therefore, in the present work we propose a new approach to the synthesis of 1,6‐disubstituted tetrahydropyrimidine‐2(1H)‐ones via the acid‐catalyzed reaction of (3,3‐diethoxypropyl) urea with various phenols. The proposed approach allows to obtain target compounds in one‐pot manner and without the use of expensive reagents and catalysts. [ABSTRACT FROM AUTHOR]

Pyrrolidine-based phosphonates, analogues of the natural amino acid proline, possess a diverse set of biological activity. The goal of this short review is to summarize the major developments in the synthesis of phosphaproline derivatives reported since 2004 with special emphasis on the mechanisms and limitations of the methods presented. 1 Introduction 2 Phosphorylation of Pyrrolidine Derivatives 2.1 Syntheses via Pudovik Reaction 2.2 Syntheses via Arbuzov Reaction 2.3 Decarboxylative Phosphorylation of Proline 2.4 Direct C–H Bond Phosphorylation 2.5 Other Reactions 2.6 Overview of Phosphorylation Methods 3 Synthesis of 2-Phosphorylpyrrolidines from Acyclic Precursors 3.1 Cyclization of 4-Substituted Butylamine Derivatives 3.2 [3+2]-Dipolar Cycloaddition of α-Iminophosphonates 3.3 Cyclization of Aminoalkynes and 4-Aminocarbonyl Compounds 4 Conclusions [ABSTRACT FROM AUTHOR]

A first successful synthesis of 2‐(pyrazolyl)pyrrolidines is reported starting from readily available reagents. A wide variety of N‐substituted 2‐(pyrazolyl)pyrrolidines are obtained with up to 96 % yield. The influence of the obtained compounds on biofilm formation by V. aquamarinus DSM 26054 and A. calcoaceticus VKPM B–10353 have been studied. Some of the tested compounds were found to suppress the growth of bacterial biofilms at nanomolar concentrations and thus are promising candidates for further studies. [ABSTRACT FROM AUTHOR]

2‐(Hetero)arylpyrrolidine fragment is found in a diverse array of biologically active molecules, both natural and unnatural. In recent years, a substantial increase in number of approved drugs featuring this scaffold is observed. Developing methods for the synthesis of such compounds has been essential for making progress in this field. Most of these methods require usage of metal catalysts and introduce additional chemical steps to obtain appropriately substituted starting compounds. This microreview details the one‐pot approach for the synthesis of pyrrolidine derivatives possessing (hetero)aromatic substituent at the second position of pyrrolidine ring based on usage of readily available N‐substituted 4,4‐diethoxybutan‐1‐amines and (hetero)aromatics as starting compounds and Bronsted acids as catalysts. [ABSTRACT FROM AUTHOR]

Herein, we report the approach to the otherwise hardly accessible dibenzoxanthenes, diarylbutanes, and calix[4]resorcinarenes possessing urea moieties based on the reaction of N-(4,4-diethoxybutyl)ureas with electron-rich aromatics in strongly acidic media. Unlike the previously developed methods, the proposed approach benefits from one-pot procedure and allows to obtain the target compounds with much higher yields. [ABSTRACT FROM AUTHOR]

Herein, we report the successful application of a novel approach to 2-substituted pyrrolidines based on intramolecular cyclization/intermolecular Mannich-type cascade reaction of N-(4,4-diethoxybutyl)sulfonamides to the synthesis of pyrrolidines possessing heterocyclic and polyaromatic moieties. The proposed approach benefits from mild reaction conditions, moderate to high yields of target compounds and provides a convenient route to the previously unknown 1-sulfonyl-2-arylpyrrolidines. [ABSTRACT FROM AUTHOR]

In this article, we report the approach to the substituted ureas based on the reaction of 1-(3,3-diethoxypropyl)ureas with phenols. Depending on the nature of the phenol and urea the reaction leads either to diarylpropane and dibenzoxanthene derivatives or calixarenes. The proposed method benefits from mild reaction conditions, high product yields and operational simplicity. [ABSTRACT FROM AUTHOR]

The reactions of N-(4,4-diethoxybutyl)amidophosphates with С-nucleophiles in chloroform in the presence of trifluoroacetic acid provided new 2-hetarylpyrrolidines. The reaction proceeded under mild conditions and gave good yields in the absence of metal-based catalysts. [ABSTRACT FROM AUTHOR]

Abstract: Reaction of nitrogen-containing acetals with aromatic compounds is a valuable method of synthesis of various heterocycles. Herein we report the study on the reaction of (4,4-diethoxybutyl)ureas with nucleophilic aromatics. We have found that the structure of the products mainly depends on the strength of the acid used as catalyst as well as aromatic nucleophile nature and its concentration. Either 2-arylpyrrolidines, diarylbutanes, bispyrrole derivatives, or pyrrolidinequinazolinones can be synthesized via variation of these factors. The proposed mechanism of the reaction is discussed.Graphical abstract: [ABSTRACT FROM AUTHOR]

The rare example of pyrrolidine C-N bond cleavage in 1-sulfonylpyrrolidines in acidic media in the presence of phenols is reported. The reaction proceeds under mild conditions and provides a convenient route to otherwise hardly accessible and previously unknown dibenzoxanthenes, diarylbutanes, and resorcinarenes having a sulfonylamide moiety. [ABSTRACT FROM AUTHOR]

Herein we report our studies on the acid-catalyzed cyclisation of N-(4,4-diethoxybutyl)sulfonamides at the presence of polyatomic phenols as an efficient one-pot approach to the synthesis of 1-sulfonyl-2-arylpyrrolidines from the acyclic precursors. [ABSTRACT FROM PUBLISHER]

The review summarizes methods of synthesis of 3-arylidenepyrrolidines, illustrated by the most typical examples, published in 2017–2019. The methods are divided into three main groups: modification of the 1-pyrroline (pyrrolidine) ring, intramolecular and intermolecular cyclization of unsaturated acyclic precursors. [ABSTRACT FROM AUTHOR]

This article provides an overview of the most typical strategies and methods applicable for the synthesis of hetaryl-substituted pyrrolidine derivatives, published between 2016 and 2018. The described methods are divided into two main groups: the introduction of heterocyclic substituent in pyrrolidine or its derivatives and the assembly of pyrrolidine ring containing hetaryl substituents from appropriately substituted acyclic precursors. [ABSTRACT FROM AUTHOR]

1-(4,4-Diethoxybutyl)-3-alkylureas undergo intramolecular cyclization in the presence of trifluoroacetic acid and various phenols, leading to the new N-alkyl-2-arylpyrrolidine-1-carboxamides with moderate to excellent yields. It was found that these compounds undergo spontaneous solid-phase epimerization at room temperature. Advantages of the proposed approach are mild reaction conditions and no need for expensive reagents or catalysts. [ABSTRACT FROM AUTHOR]

A series of novel 4-(het)arylimidazoldin-2-ones were obtained by the acid-catalyzed reaction of (2,2-diethoxyethyl)ureas with aromatic and heterocyclic C-nucleophiles. The proposed approach to substituted imidazolidinones benefits from excellent regioselectivity, readily available starting materials and a simple procedure. The regioselectivity of the reaction was rationalized by quantum chemistry calculations and control experiments. The anti-cancer activity of the obtained compounds was tested in vitro. [ABSTRACT FROM AUTHOR]

New water soluble 1-vinylsulfonyl-2-arylpyrrolidine derivatives were obtained through aza-Michael reaction of 4-chloro-6-[1-(vinylsulfonyl)pyrrolidin-2-yl]benzene-1,3-diol with secondary aminophosphonates in water-ethanol medium in the presence of triethylamine. [ABSTRACT FROM AUTHOR]

To the article "Synthesis of novel macrocyclic and heterocyclic taurine derivatives based on the reaction of sodium 2-[(4,4-diethoxybutyl)amino]ethanesulfonate with phenols" by Andrey V. Smolobochkin, Lola Zh. Yakhshilikova, Almir S. Gazinov, Liliya I. Vagapova, Alexander R. Burilov, Michael A. Pudovik [ABSTRACT FROM AUTHOR]