Current Organic Chemistry - Volume 23, Issue 19, 2019

This review summarizes the data published on the methods of preparation of β- keto amides as a versatile synthon for many heterocyclic rings and asymmetric urea derivatives. Based on the starting materials used for the synthesis of β-keto amides, eight methods were reported including β-keto acids and their derivatives, Meldrum’s acid and their derivatives, diketene, 2,6-dimethyl-1,3-dioxin-4-one derivatives (TMD), α-diazo ketones, enamines and enolates, acetamides and their derivatives and reduction of certain Passerini products.

In recent years, the synthesis and evaluation of the biological properties of 1,2,4,5-tetrasubstituted-1H-imidazole derivatives have been the subject of a large number of studies by academia and industry. In these studies it has been shown that this large and highly differentiated class of heteroarene derivatives includes high valuable compounds having important biological and pharmacological properties such as antibacterial, antifungal, anthelmintic, anti-inflammatory, anticancer, antiviral, antihypertensive, cholesterol-lowering, antifibrotic, antiuricemic, antidiabetic, antileishmanial and antiulcer activities. The present review with 411 references, in which we focused on the literature data published mainly from 2011 to 2017, aims to update the readers on the recent developments on the synthesis and biological evaluation of pharmacologically relevant 1,2,4,5-tetrasubstituted-1H-imidazole derivatives with an emphasis on their different molecular targets and their potential use as drugs to treat various types of diseases. Reference was also made to substantial literature data acquired before 2011 in this burgeoning research area.

O-Acylated 2,2,6,6-tetramethylpiperidine-N-oxyls (abbr. O-AcylTEMPOs) are easily available and stable carboxylic derivatives, but their utility in organic synthesis is unexplored in contrast to analogues, such as the N-methoxy-N-methylamides, known as Weinreb amides. Especially, the O–N unit of the O-acylTEMPOs dictates a fairly electronwithdrawing character for the carbonyl function. This enhances the reactivity and stability of the resulting enolate ions. Accordingly, O-acylTEMPOs allow various transformations and this review encompasses seven topics: (1) Reactivity of O-acylTEMPOs towards nucleophiles and chemoselective transformations, (2) Reactivity of anionic species derived from O-acylTEMPOs, (3) E-Selective Knoevenagel condensation of acetoacetylTEMPOs and synthesis of furans, (4) Electrocyclization of 2,4-dienones derived from acetoacetic derivatives and 2-substituted enals, (5) Diastereoselective addition of amide anion to O-(2-alkenoyl)TEMPOs and β-amino acid synthesis, (6) Thermolysis of O-acylTEMPOs, and (7) Applications for Umpolung reactions using O-benzoylTEMPOs, useful for the electrophilic amination of alkenes and alkynes.

Currently, peptide nucleic acids (PNAs) play an important role as therapeuticAhmed S. Abdelbaky1,2,*, Ivan A. Prokhorov1, Elena V. Gnuskova1, Olga V. Esipova1 and Yulia G. Kirillova1 agents, molecular tools for diagnosis and detection of genetic diseases as well as in biosensor probes. This research aims to optimize the synthesis of aeg- and γ-(S)-Me PNA monomers based on L-Ala, intended for oligomerization according to the Boc protocol. The monomers were obtained through the condensation of the corresponding pseudopeptides with carboxymethyl purine nucleic bases. During the work, the optimization of benzyloxycarbonyl- N6-adenine-9-yl-acetic acid and benzyloxycarbonyl-N2-guanine-9-ylacetic acid was carried out. The synthesis of benzyloxycarbonyl-N6-adenine-9-yl-acetic acid was conducted in three stages based on adenine with an overall yield of 22%. At the same time, the conditions for effective recrystallization of the mixture after alkylation of benzyloxycarbonyl-N6-adenine with ethyl bromoacetic acid ether have been developed to isolate the desired N9-regioisomer. Also, the optimization of a known method for producing benzyloxycarbonyl-N2-guanine-9-ylacetic acid from 2-amino-6-chloropurine was carried out. The total yield of the five-stage scheme was 55%. Condensation of aeg- and γ-(S)-Me pseudopeptides with benzyloxycarbonyl-N6-adenine-9-yl-acetic acid and benzyloxycarbonyl-N2-guanine-9-yl-acetic acid was performed by the standard carbodiimide method, DCC/HOBt in DMF followed by the removal of C-terminal methyl protective group by alkaline hydrolysis. The structure of the new compounds obtained was confirmed by spectral analysis methods. This work provides simple and optimized methods for obtaining protected carboxymethyl purine bases and increasing the efficiency of the synthesis and synthesized purine PNA monomers in an acceptable yield.

Triterpenes and phytosterols are classes of natural compounds widespread in plants possessing a great number of pharmacological activities. In our continued search for new compounds from natural sources with pharmacological potential, we prepared a series of novel stigmasterol and ursolic acid (UA) derivatives by coupling with L-proline, L-cysteine and L-glutamic acid. Unlike stigmasterol, the eight derivatives obtained showed good inhibitory capacity against acetylcholinesterase (AChE) or prolyl oligopeptidase (POP). Among these derivatives, we highlight 3 and 5 with IC50 values of 99.0 ± 8.8 and 97.5 ± 5.0 μM against AChE, respectively, and derivative 8 with a POP IC50 value of 75.7 ± 6.3 μM. The ursolic acid derivative 19 was the most promising compound of its class, with IC50 against AChE of 98.3 ± 7.7 μM. These results demonstrate that simple structural modifications on triterpenes and phytosterols can enhance their performance as enzymatic inhibitors.

Due to an overlook the reference nos. 1, 6, 8, 15, 16, 34, 40, 41, 46, 47, 48, 68, 74, 80, 81 & 96 were published erroneously in the article, entitled: “Newer Developments in the Synthesis of P-Heterocycles” in “Current Organic Chemistry”, 2019, Vol. 23, No. 12, pp. 1342- 1355.”