Traceless synthesis of 3-N-substituted-2-thioxoquinazoline-4-ones on a soluble polymeric support

The synthesis of 3-N-substituted-2-thioxoquinazoline-4-ones is described with a traceless linker strategy using poly(ethylene glycol) (PEG) as a soluble polymeric support. Staudinger-Aza-Wittig reaction of PEG-supported azide with Ph(3)P and CS(2) gave the corresponding PEG-supported phenyl isothiocyanate. Treatment of the phenyl isothiocyanate with different primary amines led, via intramolecular cyclization and simultaneous cleavage from PEG, to 2-thioxoquinazoline-4-ones with of moderate to excellent yields.     

Traceless synthesis of quinazoline‐2,4‐diones by curtius rearrangement reaction using poly(ethylene glycol) as soluble polymeric support

We have developed an efficient method to synthesize various quinazoline‐2,4‐diones using poly‐(ethylene glycol) as soluble polymeric support. The procedure of this reaction included: formation of acyl azide, efficient Curtius rearrangement, nucleophlic addition with amines to produce ureas, cyclization and concurrent cleavage of the resulted six‐membered heterocycle from PEG‐support in excellent yields. This method is mild and manipulation is easy.     

A novel approach to oligonucleotide synthesis using an imidazolium ion tag as a soluble support

The synthesis of oligonucleotides in solution using a soluble, ionic liquid based support is described. Short oligomers of varying base composition were synthesized using this method in high yields and high purity, requiring no chromatography for purification prior to cleavage from the support. The solution-phase-synthesized oligomers were compared to the same sequences prepared using standard gene machine techniques by LCMS. This methodology may provide a cheaper route for the large-scale synthesis of oligonucleotides.     

Microwave-assisted liquid-phase synthesis of methyl 6-amino-5-cyano-4-aryl-2-methyl-4H-pyran-3-carboxylate using functional ionic liquid as soluble support

A microwave-assisted liquid-phase synthesis of methyl 6-amino-5-cyano-4-aryl-2-methyl-4H-pyran-3-carboxylate was developed using functional ionic liquid as soluble support. IL-bound acetoacetate was treated with arylidenemalononitriles to give supported 4H-pyran derivatives. After cleavage, the target compounds were obtained in good yields and high purities without chromatographic purification.     

Traceless solid-phase synthesis of 1,2,4-triazoles using a novel amine resin

[reaction: see text]. A solid-phase route to 5-aryl-3-arylthiomethyl-1,2,4-triazoles has been developed that permits the incorporation of two elements of diversity. The heterocycle was constructed upon a novel 4-benzyloxy-2-methoxybenzylamine (BOMBA) resin, from which traceless cleavage could be effected with dilute TFA. A library of 96 triazoles was produced with an average yield of 26% (84% yield per step) and an average purity of 80%. In a direct comparison, the new BOMBA resin proved to be markedly superior to Rink Amide resin for this application.     

Traceless liquid-phase synthesis of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles on polyethylene glycol (PEG)

A liquid-phase route to 3-alkylamino-4,5-disubstituted-1,2,4-triazoles has been developed, which permits the incorporation of three elements of diversity. The heterocycle was constructed upon PEG6000 (soluble polymer) modified by 4-hydroxy-2-methoxybenzaldehyde, from which a traceless cleavage could be realized with TFA/CH₂Cl₂. This method provided a library of 3-alkylamino-4,5-disubstituted-1,2,4-triazoles with reasonable yields and excellent purity.     

Parallel synthesis of 4,5-dihydro-1,2,4-oxadiazoles using soluble polymer support

1,3-Dipolar cycloadditions of nitrile oxide generated in situ on soluble polymer with a variety of imines provided a library of 4,5-dihydro-1,2,4-oxadiazoles in good yields and purity.     

Efficient synthesis of 4(3H)-quinazolinones using a soluble polymeric support

4(3H)-Quinazolinones have been synthesized from poly(ethylene glycol)(PEG)supported aza-Wiuig reaction.2-Dialkylamino- 4(3H)-quinazolinones 6 were synthesized efficiently by reaction of secondary amine with PEG-supported carbodiimides 4,which were obtained from aza-Wittig reaction of PEG-supported iminophosphoranes 3 with isocyanates.     

Synthesis and mesomorphic properties of 4-alkyl-3,4'-disubstituted biphenyls and terphenyls

Liquid-crystalline 4-alkyl-3-chloro(methyl)-4'-substituted biphenyls and terphenyls have been synthesized. Investigation of the mesomorphic properties of these compounds shows that unlike their unsubstituted analogues they form a liquid-crystalline phase at a lower temperature and over a narrower temperature range.     

Traceless solid-phase synthesis of bicyclic dihydropyrimidones using multidirectional cyclization cleavage

Solid-phase and solution-phase protocols for the synthesis of furo[3,4-d]pyrimidines, pyrrolo[3,4-d]pyrimidines, and pyrimido[4,5-d]pyridazines are reported. The multistep solid-phase sequence involves the initial high-speed, microwave-promoted acetoacetylation of hydroxymethylpolystyrene resin with methyl 4-chloroacetoacetate. The immobilized 4-chloroacetoacetate precursor was subsequently subjected to three-component Biginelli-type condensations employing urea and a variety of aromatic aldehydes. The resulting 6-chloromethyl-functionalized resin-bound dihydropyrimidones served as common chemical platforms for the generation of the desired heterobicyclic scaffolds using three different traceless cyclative cleavage strategies. The corresponding furo[3,4-d]pyrimidines were obtained by microwave flash heating in a rapid, thermally triggered, cyclative release. Treatment of the chloromethyl dihydropyrimidone intermediates with a variety of primary amines followed by high-temperature microwave heating furnished the anticipated pyrrolo[3,4-d]pyrimidine scaffolds via nucleophilic cyclative cleavage. In a similar way, reaction with monosubstituted hydrazines resulted in the formation of pyrimido[4,5-d]pyridazines. All compounds were obtained in moderate to good overall yields and purities.     

An efficient approach to the synthesis of water-soluble cyanine dyes using poly(ethylene glycol) as a soluble support

An efficient synthesis approach to unsymmetrical water-soluble cyanine dyes has been established. Loading and activation of sulfoindolenium to poly(ethylene glycol) (PEG) have been achieved via a simple strategy. Cyanine dyes are released by the attack of heterocyclic carbon nucleophile and the cleavage of PEG-bound hemicyanine. The efficient approach delivers cyanine dyes in high purity without the nontrivial chromatographic separation.     

Liquid-phase parallel synthesis of 2-aryl-5-methoxylcarbonyl-dihydropyrones using soluble polymer support

General and efficient methods for the construction of 2-aryl-5-methoxylcarbonyl-dihydropyrones on soluble polymer support have been developed. The hetero-Diels-Alder reaction of aldehydes with poly(ethylene glycol) (PEG)-bound Danishefsky’s diene derived from PEG-bound acetoacetate, followed by cleavage from the support, afforded 2-aryl-5-methoxylcarbonyl-dihydropyrones. The products were obtained in good yields and high enantioselectivities.     

Parallel synthesis of novel benzimidazoles on a soluble polymer support

Liquid phase combinatorial synthesis using a soluble polyethylene glycol (PEG) polymer support and commercially available 3-nitro-4-fluoro benzoic acid is carried out in order to create a molecular library of trisubstituted benzimidazoles. The PEG-ester conjugate of 3-nitro-4-fluoro benzoic acid is subjected to ipso-fluoro displacement by various primary amines. The nitro group is reduced under neutral conditions using excess zinc and ammonium chloride, producing the polymer-boundo-phenylene diamines. Reaction of the diamines with different aldehydes results in cyclisation to benzimidazoles. The polymer support is cleaved releasing the desired products in high yields and purity. All reactions are performed at room temperature.      

A practical and general synthesis of unsymmetrical terphenyls

A synthetic procedure was developed that enables sequential chemoselective Suzuki-Miyaura cross-coupling of chlorobromobenzene with arylboronic acids. The first coupling is achieved at room temperature using a ligandless palladium catalyst. The chlorobiaryl product can then be subjected directly to the second coupling, facilitated by the SPhos ligand. Using this methodology, parallel synthesis of 32 unsymmetrical o-, m-, and p-terphenyl compounds was accomplished in good to excellent overall yields.     

可溶性聚合物在有机合成中的应用研究

概述了液相合成中所使用的可溶性聚合物性质、类型、特点,以及可溶性聚合物在合成肽、低聚苷酸、寡糖、杂环化合物、催化剂、试剂及小分子物质等方面的应用。     

A novel approach for synthesis of 3-amino-5-aryl-2,5-dihydropyridazines using onium salt as soluble support

In this work it was presented an application of task specific onium salt as soluble support for the synthesis of 3-amino-5-aryl-2,5- dihydropyridazines.This soluble support is of wide applicability and combines advantages of solid phase synthesis without its limitations with those of solution phase chemistry.After a simple washing step,products were cleaved from the supports and obtained in good yields.     

Efficient synthesis and properties of soluble aliphatic oligo(spiroorthocarbonate)s from pentaerythritol derivatives

A series of soluble oligo(spiroorthocarbonate)s (OSOCs) were synthesized by polycondensation of tetraethylorthocarbonate with pentaerythritol derivatives. The pentaerythritol derivatives used herein were synthesized from pentaerythritol by attaching substituents on it to improve the solubility of themselves and the resulting OSOCs. The structures of the OSOCs were confirmed by NMR spectroscopy and MALDI‐TOF mass analysis. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 792–798