4-羟基-2-吡啶酮类化合物的合成研究进展

4-羟基-2-吡啶酮是天然生物碱结构母核,同时也是一类重要的医药中间体,该类衍生物具有抗真菌、抗菌和抗肿瘤等多种生物活性.因此,其合成得到了广泛的研究和关注.综述了近年来4-羟基-2-吡啶酮类化合物的合成方法及其研究进展.     

Three-step synthesis of 4-(2′-hydroxyethyl) azetidin-2-one and its substituted derivatives from 4-acetoxy-2-pyridones

4-(2'-Hydroxyethyl)azetidin-2-one, an important synthetic intermediate for carbapenem, and its substituted derivatives have been synthesized from 4-acetoxy-2-pyridones by photolysis, catalytic hydrogenation, followed by basic hydrolysis in the presence of sodium borohydride.     

Chelate method for the synthesis of 3-amidino-substituted 4-pyridones

Russian Chemical Bulletin - An efficient synthetic procedure to obtain 3-(N-benzoylamidino)-substituted 4-pyridones has been developed based on the reaction of difluoroboron complex of...     

Facile route to 1-phosphoryl- and 1-sulfonyl-1,3-dienes via palladium-catalyzed elimination of allylic acetates

The palladium(II)-catalyzed chloroacetoxylation of 1,3-dienes is employed to prepare 1-chloro-4-acetoxy-2-alkenes which are then transformed into 1-phosphoryl- or 1-sulfonyl-4-acetoxy-2-alkenes respectively. Elimination of acetate is promoted by palladium(O)-catalysis or by sodium hydride, producing the useful 1-phosphory]- or 1-sulfonyl-1,3-dienes.     

The diene synthesis reaction and substitutive addition with 2-pyridones and their thio analogs (review)

The literature on the reactions of 2-pyridones and their thio analogs with unsaturated compounds taking place by a mechanism of diene synthesis or of substitutive addition, depending on the structure of the initial components, has been systematized. The basic synthetic directions of the use of these reactions and also the stereochemistry of the diene synthesis with 2-pyridones and 2-thiopyridones are considered.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 3–20, January, 1984.     

Approach to Polysubstituted 4-Pyridones from N-Aryl Acetoacetamides via a N to C 1,3-Acyl Migration Mediated by Sodium Persulfate

Mediated by sodium persulfate (Na(2)S(2)O(8)), a series of polysubstituted 4-pyridones were synthesized via self-condensation of N-aryl acetoacetamides, during which a novel N to C 1,3-acyl migration should be involved. The structure of 4-pyridone was unequivocally confirmed by X-ray diffraction analysis. However, the self-condensation of N-benzyl acetoacetamides under the same condition gave polysubstituted 2-pyridones instead of 4-pyridones.     

Synthesis of 2,4-disubstituted N-acyl-5,6-dihydro-2-pyridones

A simple two-step procedure converts 2-substituted N-acyl-2,3-dihydro-4-pyridones to 2,4-disubstituted N-acyl-5,6-dihydro-2-pyridones.     

Cycloaddition of 2(1H)-pyridones having a methoxycarbonyl group to 1,3-butadiene derivatives

The cycloaddition of 4-methoxycarbonyl-2(1H)-pyridones to silyloxydienes gave isoquinolone derivatives in reasonable yields. Furthermore, the cycloaddition of 6-methoxycarbonyl-2(1H)-pyridones to 2,3-dimethyl-1,3-butadiene produced cycloadducts (isoquinolone and quinolone derivatives) and double cycloadducts (phenanthridone derivatives). The activation energies using Gaussian 98 with RHF/3-21G level of 4- and 6-methoxycarbonyl-2(1H)-pyridones coincided with the experimental facts.     

4-羟基-2-吡啶酮类天然生物碱的研究进展

4-羟基-2-吡啶酮类生物碱是从植物和昆虫等内生真菌发酵液中提取分离得到的一类新型天然生物碱, 具有抗真菌、抗菌和抗肿瘤等多种生物活性. 对近年来4-羟基-2-吡啶酮类天然生物碱的分离、结构确证和全合成等进行了总结和概述, 重点介绍了Ilicilolin H, Tenellin和Sambutaxin等的全合成.     

General synthetic methods for the preparation of 1-substituted-vinyl-2-pyridones

General methods for the preparation of a variety of 1-substituted vinyl-2-pyridones are described. Synthetic routes followed involve (1) nucleophilic substitution reaction of the 2-hydroxy-pyridyl anion of haloolefins containing β-activating groups, such as carbonyl and phenyl, (2) elimination reactions of ester derivatives of 1-pyridonyl-2-ethanols and (3) base catalyzed isomerizations of 1-allyl-2-pyridones. The details involved with each of the synthetic methods and purification of the derived 1-vinyl-2-pyridones are described. Additionally important spectroscopic properties of compounds in this series are discussed in terms of preferred conformations about the nitrogen-exocyclic vinyl carbon bond.     

Retro-ene reactions in heterocyclic synthesis. II. A facile synthetic method for 4-hydroxy-2-pyridones

Schiff's bases 1 derived from ketones and t-butylamine reacted with diphenyl malonate, diphenyl methyl-malonate and diphenyl phenylmalonate to give 4-hydroxy-2-pyridones 4–6 . Schiff's bases b on reaction with trimethyl methanetricarboxylate afforded 4-hydroxy-3-methoxycarbonyl-2-pyridones 12 .     

Intramolecular rearrangement of two-ring 2,2-disubstituted 4-oxo-1,2,3,4-tetrahydropyrimidines under the influence of polyphosphoric acid

Intramolecular rearrangement of two-ring 2,3-disubstituted 4-oxo-1,2,3,4-tetrahydropyrimidines to pyridine derivatives, which takes place under the influence of polyphosphoric acid, was observed. It is shown that cycloalkanopyrimidones are converted primarily to two- or three-ring 2-pyridones and to small amounts of the corresponding 4-pyridones and 4-aminopyridines. A possible mechanism that enables one to explain the difference in the occurrence of the rearrangements primarily to 2- or 4-pyridones as a function of the absence or presence of aromatic character of the ring condensed with the pyrimidine ring is proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1549–1553, November, 1977.     

Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Abeta-peptide aggregation inhibitors

A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on Abeta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer Abeta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric Abeta-peptide.     

5，6－二取代－3，4－二氢－2－吡啶酮的N－烷基化反应

由四个５，６－二取代－３，４－二氢－２－吡啶酮经烷基化反应合成了九个未见文献报道的Ｎ－取代５，６－二取代－３，４－二氢－２－吡啶酮，并确定了它们的结构。     

Light-induced enantiospecific 4π ring closure of axially chiral 2-pyridones: enthalpic and entropic effects promoted by H-bonding

Nonbiaryl axially chiral 2-pyridones were synthesized and employed for light-induced electrocyclic 4π ring closure leading to bicyclo-β-lactam photoproducts in solution. The enantioselectivity in the photoproducts varied from 22 to 95% depending on the reaction temperature and the ability of the axially chiral chromophore to form intramolecular and/or intermolecular H-bonds with the solvent. On the basis of the differential activation parameters, entropic control of the enantiospecificity was observed for 2-pyridones lacking the ability to form H-bonds. Conversely, enthalpy played a significant role for 2-pyridones having the ability to form H-bonds.     

Recent advances in synthesis of 2-pyridones: a key heterocycle is revisited

Owing to the versatile applications in different areas including biology, natural compounds, dyes, and fluorescent materials, the synthesis of 2-pyridone compounds is an important research field and has attracted a great deal of attention. In this review, 2-pyridones new synthetic methods are classified to tree classes including reactions based on pyridine rings, cyclization, and cycloaddition reactions.     

Addition of indolyl and pyrrolyl grignard reagents to 1-acylpyridinium salts

Certain indolyl and pyrrolyl Grignard reagents add to 1-acyl salts of 4-methoxy-3-(triisopropylsilyl)pyridine to give the corresponding 1-acyl-2-heteroaryl-2,3-dihydro-4-pyridones in good to high yield. When the 1-acyl group contained a chiral auxiliary, (+/-)-trans-2-(alpha-cumyl)cyclohexyloxy, addition of the indolyl Grignards resulted in a separable mixture of diastereomeric 2,3-dihydro-4-pyridones.     

Cooperative 4-pyridone H-bonds with extraordinary stability. A DFT molecular orbital study

The N-H...O H-bonding enthalpy between 4-pyridones connected in a chain of H-bonds can achieve 23 kcal/mol for the most central H-bonds, while that between two 4-pyridones is 9.90 kcal/mol based upon DFT calculations on the counterpoise-corrected potential energy surfaces. That the range of enthalpies for N-H...O H-bonds can vary from as little as 2 to as much 23 kcal/mol depends primarily upon the polarizability of whatever internally connects the N-H and C=O within the H-bonding molecule, which are two parallel -C=C- entities in 4-pyridone. The contribution of covalent or charge-transfer interactions between the pi-systems of adjacent 4-pyridones is small.     

Ring transformations of 4H-pyrans. Pyridines from 2-amino-4H-pyrans

Ring transformations of 4H-pyrans into pyridines are reported. Treatment of 2-amino-4,6-diaryl-3,5-dicyano-4H-pyrans (I) with nitrosylsulfuric acid brings about their transformation into 3,5-dicyano-4,6-diaryl-2-pyridones (VI) which can also be obtained from α-benzoylcinnamonitriles (IX) and cyanoacetamide. Similarly, 2-amino-4,6-diaryl-5-carbethoxy-3-cyano-4H-pyrans (II) lead to 4,6-diaryl-5-carbethoxy-3-cyano-2-pyridones (VII). Treatment of both series of pyrans with sulfuric acid results in the formation of the corresponding 3,4-dihydro-2-pyridones (IV and V). Reaction of pyrans II with ammonium acetate in acetic acid yields 2-amino-4,6-diaryl-5-carbethoxy-3-cyanopyridines (XII). Pyrans I undergo an entirely different type of reaction upon treatment with this reagent leading to 2,4,6-triaryl-3,5-dicyano-1,4-dihydropyridines (XV).     

Diene synthesis with 2-pyrones and 2-pyridones XIV. 1,4-Cycloadducts of 1-alkyl-2-pyridones with N-phenylmaleinimide and maleinimide

1-Alkyl-2-pyridones react with N-phenylmaleinimide and maleinimide stereoselectively via the scheme of the diene synthesis to give imides of 8-alkyl-8-azabicyclo[2.2.2]-4-octen-7-one-1,2-dioic acid. 3-Unsubstituted 2-pyridones form adducts with an endo configuration, whereas 1,3-dimethyl-2-pyridone gives an exo adduct under the same conditions. The endo- and exo-bridge adducts readily undergo retrograde diene disintegration on heating.