Ugi multicomponent reaction with hydroxylamines: an efficient route to hydroxamic acid derivatives

Ugi condensations with O-protected hydroxylamines have been successfully performed in THF using ZnCl₂ as activating agent. This synthetic strategy opens up the route to a very convergent assemblage of `internal' hydroxamic acid derivatives (N-acyl-N-hydroxypeptides).     

改进的Ugi法应用于胺烷基二茂铁衍生物的合成

选择不同的按或酰胺组分, 利用改进的Ugi法合成了一系歹含有烷胺烷基、芳胺烷基或酰胺烷基的二茂铁衍生物, 研究了反应的投料比, 反应底物, 反应温域等因素对反应的影响, 并对反应机理进行了探讨。     

One-step synthesis of N-acetylcysteine and glutathione derivatives using the Ugi reaction

Fully protected natural and unnatural N-acetylcysteine, dipeptide Cys-Gly, glutathione, and homoglutathione derivatives were synthesized by the Ugi four-component reaction using various benzylthio aldehydes and ketones as carbonyl building blocks. The scope and limitations of the method were investigated. Formation of imidazoline by-products in the Ugi reaction was discussed. 2,2,2-Trifluoroethanol was shown to be a superior reaction media than methanol in some reactions. Also, the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octyl derivative (OBO-ester) of isocyanoacetic acid was shown to be superior to use than ethyl isocyanoacetate as a peptide synthesis precursor in cases when higher reactivity of an isocyanide is required.     

Synthesis of 11-aza-artemisinin derivatives using the Ugi reaction and an evaluation of their antimalarial activity

A series of new 11-aza-artemisinin derivatives were prepared from 11-aza-artemisinin using the Ugi reaction. An antimalarial activity evaluation against the FcB1 strain indicated that compounds 7, 10, and 16 had very strong inhibitory activity. Comparison of the activity among the synthetic derivatives of this series revealed that the length of the side chain R group on the amide nitrogen could be critical for their antimalarial properties.     

A facile synthesis of 1,4-benzodiazepine derivatives via Ugi four-component condensation

A simple two-step route to 4,5-dihydro-3H-benzo[1,4]diazepin-5-ones is described. This synthesis, based on the isocyanide chemistry, allows a wide variety of substitution patterns starting from commercially available or easily obtainable reagents.     

Application of Ugi three component reaction for the synthesis of quinapril hydrochloride

Abstract

A novel, efficient and concise synthesis of chirally pure quinapril hydrochloride is described. The key step is the formation of α-amino amide backbone in one step using Ugi three component reaction. This method allows short access to α-amino amide chain which is a part of many drugs used for treatment of high blood pressure. A large molecular library can be synthesized by changing the components in Ugi reaction.     

The Ugi reaction with 2-substituted cyclic imines. Synthesis of substituted proline and homoproline derivatives

The Ugi three-component reaction with 2-substituted five-, six-, and seven-membered cyclic imines was investigated. The reaction opens a new route to substituted proline and homoproline derivatives. It was shown that the method is efficient for the one-step preparation of seminatural dipeptides containing natural amino acid residues, and fragments of substituted proline or pipecolinic acid. The scope and limitation of the approach are discussed.     

Ugi reaction for the synthesis of 4-aminopiperidine-4-carboxylic acid derivatives. Application to the synthesis of carfentanil and remifentanil

A two-step sequence involving an Ugi four-component reaction was developed for the preparation of 4-aminopiperidine-4-carboxylic acid derivatives. This strategy has led to the successful preparation of two drugs carfentanil and remifentanil in shorter times and better yields than previously described methods.     

U-4C-3CR versus U-5C-4CR and stereochemical outcomes using suitable bicyclic β-amino acid derivatives as bifunctional components in the Ugi reaction

Intramolecular Ugi reactions with bicyclic β-amino acids have been performed and the effects of the configuration and N-alkylation have been studied. We have proven that preferential ring contraction or nucleophilic attack by the solvent depend not only on the presence of N-alkylation but also on the relative disposition of the carboxyl group and the amine. Excellent results in terms of stereoselectivity have been obtained in the case of N-alkyl-3-exo-amino-7-oxabicyclo[2.2.1]-2-endo-carboxylic acids.     

A versatile approach to hybrid thiadiazine-based molecules by the Ugi four-component reaction

Aiming at developing a versatile method for the generation of hybrid heterocyclic molecules, we describe a sequential approach comprising the formation of carboxy-functionalized 1,3,5-thiadiazines followed by the Ugi reaction with variation of the amino and the isonitrile components. The method enables the generation of structurally diverse molecular hybrids including peptide, lipid, steroidal and sugar moieties linked to the 1,3,5-thiadiazine scaffold.     

One-pot and regioselective synthesis of polysubstituted 3,4-dihydroquinazolines and 4,5-dihydro-3H-1,4-benzodiazepin-3-ones by sequential Ugi/Staudinger/aza-Wittig reaction

An efficient one-pot and regioselective synthesis of 3,4-dihydroquinazolines and 4,5-dihydro-3H-1,4-benzodiazepin-3-ones by Ugi/Staudinger/aza-Wittig sequence has been developed. The Ugi reactions of 2-azidobenzylamines, aldehydes, acids (or α-keto acids) and isocyanides produced the azide intermediates, which were then treated with tributylphosphine or triphenylphosphine to give polysubstituted 3,4-dihydroquinazolines or 4,5-dihydro-3H-1,4-benzodiazepin-3-ones in moderate to good yields by tandem Standinger/aza-Wittig reactions.     

A simple synthesis of ferrocenyl bis-amides by a Ugi four-component reaction

An efficient and simple synthesis of ferrocenyl bis-amides by the Ugi four-component reaction of ferrocenecarboxaldehyde, carboxylic acids, isocyanides and amines in methanol at room temperature is reported.     

Application of Mn(III)-catalysed olefin hydration reaction to the selective functionalisation of avermectin B1

The Mn(dpm)₃-catalysed olefin hydration reaction of α,β-unsaturated esters and ketones discovered by Mukaiyama in 1990 and further developed by Magnus in 2000 was applied to the challenging environment of avermectin B₁. Different avermectin substrates such as 4″,7-OTMS-5-oxo-avermectin B₁3, avermectin B₁1 and Δ^2,3-avermectin B₁6 were thus treated with Mn(dpm)₃, PhSiH₃ in isopropanol under oxygen atmosphere to afford several novel analogues, including 3,4-dihydro-3-hydroxy-avermectin B₁8 with high level of regio- and stereoselectivity, 2-hydroxy-3,4-dihydro-avermectin B₁7, the first example of a 2-substituted avermectin and the novel 22,23-dihydro-22-hydroxy-avermectin B₁9a and 9b, epimeric at C(22). Biological activity of these new avermectin derivatives is also reported.     

阿维菌素B1a纯物质的制备纯化研究

本研究致力于制备纯化出高纯阿维菌素B1a,为核磁定量及质量平衡法提供计量溯源纯物质,从而给阿维菌素标准物质(研制中)纯度定值时提供纯度参考标准。利用制备型液相色谱对阿维菌素原料(B1a含量为95.71%)进行纯化,除去痕量杂质,真空干燥及冷冻干燥后得到阿维菌素B1a高纯物质。建立了基于制备液相色谱-真空干燥的阿维菌素B1a高纯物质的制备纯化工艺:采用Agilent Prep HT XDB-C18型制备柱,流动相为水/甲醇(15∶85),进样量500μL,流速20.0m L/min。经超高效液相色谱(UPLC)检测,产品纯度达到99.74%,可以满足核磁定量及质量平衡法的要求,并利用液相色谱串联质谱以及核磁共振法对产品进行定性分析。     

A convergent synthesis of enantiopure bicyclic scaffolds through multicomponent Ugi reaction

An efficient and convergent Ugi synthesis of enantiomerically pure N-acyl-2,5-disubstituted pyrrolidines was coupled with an appropriate secondary transformation to give two series of bicyclic derivatives, namely hexahydro pyrrolo-oxazocinediones and -diazepinediones.     

Nano structured spinel Co3O4-catalyzed four component reaction: A novel synthesis of Ugi adducts from aryl alcohols as a key reagent

A simple one pot procedure for the synthesis of α-amino acyl amide with chromone,indole,and napthalene substitution pattern is presented.This protocol involves the nano structured spinel Co_3O_4catalysed coupling of aryl alcohols,anilines,carboxylic acids and tert-butyl isocyanide.The salient features of this protocol were simple procedure,mild reaction condition and high yield.     

Ugi/Diels-Alder串联反应在构建杂环化合物中的应用

杂环化合物广泛存在于天然产物和药物分子中,许多杂环化合物还具有潜在生物活性和药理作用。因此,如何快速高效地构建小分子杂环化合物库成为当今有机合成和药物化学领域的研究热点。Ugi反应在多样性导向合成方面具有得天独厚的优势,能够解决待合成化合物数量庞大、结构复杂的难题;同时,Diels-Alder [4+2]环加成反应能够高效构建碳-碳键,以较高的立体选择性和区域选择性合成六元环系。目前,集二者于一身的Ugi/Diels-Alder串联反应在构建杂环化合物方面展现出了巨大优势和无穷潜能。本文以不同类型的DA反应分类:按照呋喃作为双烯体、吡咯作为双烯体、噻吩为双烯体、口恶唑作为双烯体、 1,2,4-三嗪作为双烯体、苯作为双烯体、不饱和键和芳环共同作为双烯体等对UDA串联反应的研究进行了综述。     

Vitamin B1

Ohne Zusammenfassung     

Ugi reaction of thiouridocarboxylic acids: A synthesis of thiourea-peptoids

Benzoylthioureidocarboxylic acids, prepared from benzoyl chlorides, potassium thiocyanate, and α-aminoacids, are used as acid components in the Ugi reaction to produce thiourea-peptoids in moderate to good yields.