3-(2-methylthiopyridin-3-yl)-3-oxopropionic esters

A reaction of alkyl bromoacetates with substituted 3-cyano-2-methylthiopyridines in the presence of zinc dust furnishes 3-amino-3-(2-methylthiopyridin-3-yl)propenoic esters. Their hydrolysis under mild conditions leads to 3-(2-methylthiopyridin-3-yl)-3-oxopropionic esters. The latter were used in the synthesis of pyridine-substituted pyrazolones.     

Functional mapping of the 14-3-3 hub protein as a guide to design 14-3-3 molecular glues

Molecular glues represent an evolution in drug discovery, however, targeted stabilization of protein complexes remains challenging, owing to a paucity of drug design rules. The functional mapping of hotspots has been critical to protein–protein interaction (PPI) inhibitor research, however, the orthogonal approach to stabilize PPIs has not exploited this information. Utilizing the hub protein 14-3-3 as a case study we demonstrate that functional mapping of hotspots provides a triage map for 14-3-3 molecular glue development. Truncation and mutation studies allowed deconvoluting the energetic contributions of sidechain and backbone interactions of a 14-3-3-binding non-natural peptide. Three central 14-3-3 hotspots were identified and their thermodynamic characteristics profiled. In addition to the phospho-binding pocket; (i) Asn226, (ii) Lys122 and (iii) the hydrophobic patch formed by Leu218, Ile219 and Leu222 were critical for protein complex formation. Exploiting this hotspot information allowed a peptide-based molecular glue that elicits high cooperativity (α = 36) and selectively stabilizes the 14-3-3/ChREBP PPI to be uniquely developed.

The functional mapping of a 14-3-3 protein complex, by means of peptide truncations and point mutations, as an approach to identify critical hotspots regions for 14-3-3 molecular glue drug design.     

3-(Carbazol-2-yl)- and 3-(Carbazol-3-yl)-dl-alanines

A facile transformation of 2- and 3-methylcarbazoles into 3-(carbazol-2-yl)-and 3-(carbazol-3-yl)-dl-alanines compounds is described.     

Chemistry of 3-(1H-Indol-3-yl)-3-oxopropanenitrile

This review highlighted the methods used for the synthesis of different heterocyclic compounds derived from 3-(1H-indol-3-yl)-3-oxopropanenitrile. The reactivity and their synthetic importance were investigated. In this context, recent progress in the synthesis and use of 3-(1H-indol-3-yl)-3-oxopropanenitrile as precursors for heterocyclic compounds is reviewed.     

2-(Acylmethylmercapto)-3-amino- and 2-(acylmethylmercapto)-3-acetamidopyridines

The reaction of 2-mercapto-3-acetamido-5-(or 6-)chloropyridines with phenacyl bromide and substituted phenacyl bromides yielded 2-(phenacylmercapto)-3-acetamidopyridines, while the reaction of the former with -chloroacetoacetic ester yielded 2-(carbethoxyacyl-methylmercapto)-3-acetamidopyridlnes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1391–1394, October, 1971.     

3-(3＇-乙酰基-5＇-芳基-1＇,3＇,4＇-二氢噁二唑-2＇-)色酮的微波促进合成

将微波应用于促进有机合成是近年来兴起的新技术,已受到极大注意,我们采用简单的微波反应装置,成功地合成了3－杂环基取代的色酮,杂环基取代的色酮因其显著的生理活性,而成为近年来的研究特点,以3－甲酰基色酮为原料,与芳酰肼反应得到相应的芳酰腙,再用乙酸酐关环,合成了一系列3位为1,3,4－二氢恶二唑基取代的色酮（3）,为在合适的母体上引入杂环提供了一系新思路,合成路线如下。     

Synthesis of ethyl 3-(3-hydroxy-2-thienyl)-3-oxopropanoates

An approach to the synthesis of substituted ethyl 3-(3-hydroxy-2-thienyl)-3-oxopropanoates was developed based on the reaction of ethyl cyanoacetate, carbon disulfide, and ethyl 4-chloroacetoacetate. The reaction regioselectively involved the ester group, rather than the nitrile one like in the case when malononitrile or cyanacetamide were used.     

Intramolecular Diels-Alder Reactions via 3-(Phenylthio)-4-(Trimethylsilyl)-3-Sulfolene

Deprotonation of the title compound 2 followed by treatment with 5-iodo-1-pentene or 6-iodo-l-hexene gave the alkylated products 3 and 4 which upon refluxing in toluene yielded the dienes 8a and 8b. Intramolecular Diels-Alder reactions were achieved by heating the dienes 8a and 8b in toluene in a sealed tube at 160–180°C to give bicyclo[4.3.0]nonene 9 and bicyclo[4.4.0]decene 10, respectively, in good yield. The stereochemistry of the cyclization products was determined, and was rationalized by comparison of the possible transition states involved.