Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Abstract

2-Pyridone is characterized by a very wide range of reactivity of a different nature, ranging from electrophilic aromatic substitution, CH–metal-mediated reactions, and NH/OH functionalization of both possible lactam/lactim tautomers, through cycloaddition, to nucleophilic addition and transformation of the tautomeric C=O/C–OH moiety. The high availability of 2-pyridones and the possibility of their far-reaching functionalization additionally increased their values. Therefore, they are very useful building blocks for the synthesis of structurally diverse piperidine and pyridine compounds, including naturally occurring 2-pyridones. This review reports on the use of simple 2-pyridones in the synthesis of alkaloids and alkaloids-inspired compounds based on the piperidine or pyridine framework.1 Introduction2 Structure, Availability, and Reactivity of 2-Pyridones3 Monocyclic Piperidine Alkaloids from 2-Pyridones4 Polycyclic Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds from 2-Pyridones4.1 New Ring Formation Involving C/N Atoms of the 2-Pyridone Ring4.1.1 Indolizine-Fused 2-Pyridones: Camptothecins and Related Compounds4.1.2 Other Indolizines from 2-Pyridones4.1.3 Compounds Bearing the Quinolizine Ring System4.2 New Ring Formation Involving C/C Atoms of the 2-Pyridone Ring4.2.1 C-2/C-3 Ring Fusion4.2.2 C-3/C-4 Ring Fusion4.2.3 C-4/C-5 Ring Fusion4.2.4 C-5/C-6 Ring Fusion4.2.5 C-2/C-4 Ring Bridge4.2.6 C-2/C-6 Ring Bridge4.2.7 C-3/C-5 Ring Bridge4.2.8 C-3/C-6 Ring Bridge4.2.9 C-4/C-6 Ring Bridge5 Conclusion

Crystal structures and Hirshfeld surface analyses of 2-amino-4-(4-bromophenyl)-6-oxo-1-phenyl-1,4,5,6-tetrahydropyridine-3-carbonitrile hemihydrate and 1,6-diamino-2-oxo-4-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile

“…The formation of C-C, C-O, and C-N bonds is one of the essential transformation reactions of organic chemistry (Zubkov et al, 2018;Shikhaliyev et al, 2019;Viswanathan et al, 2019;Gurbanov et al, 2020). Nitrogen-containing heterocycles, especially tetrahydropyridine homologs, are wellknown heterocyclic scaffolds that exhibit a broad spectrum of biological and pharmaceutical activities (Sos ´nicki & Idzik, 2019;Sangwan et al, 2022). Being an important structural fragment of various natural products, they play a key role in cell metabolism.…”

Divergent Synthesis of Functionalized Indenopyridin-2-ones and 2-Pyridones via Benzyl Group Transfer: Two Cases of Aza-semipinacol-Type Rearrangement

“…2 They also have been applied as valuable precursors of a variety of naturally occurring and naturally inspired bioactive polycyclic piperidines. 3 Driven by the need to synthesize novel bioactive piperidine-containing polycycles, we explored 2-pyridones as a platform for obtaining benzoquinolizidine 4 and quinolizidine 5 derivatives, aryl-substituted indeno[2,1-b]pyridones (resembling the core of haouamine 6 ), indeno[2,1-c]piperidine, 7 and benzomorphanones. 8 The latter have been achieved by treatment of easily accessible 6-benzyl-3,6dihydropyridin-2(1H)-one 9 with N-bromosuccinimide (NBS) in wet CH 3 NO 2 as a solvent and with (PhO) 3 P as a catalyst (Scheme 1).…”

A Mild and Highly Diastereoselective Preparation of N-Alkenyl-2-Pyridones via 2-Halopyridinium Salts and Aldehydes

“…N -Alkyl-2-pyridones are important heterocycles encountered in various active pharmaceutical ingredients, bioactive compounds, and natural products (Figure ). − Accordingly, a diverse set of methods to prepare these valuable compounds is highly desired. ,,− While a straightforward means of obtaining N -alkyl-2-pyridones is through direct N -alkylation of 2-hydroxypyridine (2-pyridone), this method often suffers from competitive O -alkylation. ,− Methods to isomerize 2-alkoxypyridines to N -alkyl-2-pyridones ( O - to N - alkyl migration) using transition metal catalysts or Brønsted/Lewis acid promoters have also been described. ,,− ,− …”