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Review
. 2024 Jan 3;29(1):249.
doi: 10.3390/molecules29010249.

Diversity-Orientated Synthesis and Biological Properties of Compounds Based on the N-Phenylquinoneimine Scaffold

Adebimpe Adesina  1 , Rachid Skouta  2   3
Affiliations
Review

Diversity-Orientated Synthesis and Biological Properties of Compounds Based on the N-Phenylquinoneimine Scaffold

Adebimpe Adesina et al. Molecules. .

Abstract

The N-phenylquinoneimine scaffold is a versatile synthetic platform that has gained significant attention in the field of drug discovery due to its structural diversity and capacity to interact with biologically relevant targets. This review explores established synthetic methodologies and highlights the significant biological activities exhibited by compounds derived from this scaffold, their implications for medicinal chemistry, and the development of novel therapeutics.

Keywords: DNA; N-phenylquinoneimine; biological activity; diversity-orientated synthesis; drugs; reactive metabolites.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of N-phenylquinoneimine 1 (NPQ).
Figure 2
Figure 2
Some of the representative examples of quinoneimines in natural products.
Figure 3
Figure 3
Some subgroups of quinoneimine dyes.
Figure 4
Figure 4
Some of the common quinoneimine dyes.
Figure 5
Figure 5
Structure of Actinomycin D.
Figure 6
Figure 6
Some drugs that form quinoneimine reactive metabolites [56].
Scheme 1
Scheme 1
Paracetamol bioactivation to reactive species (quinoneimine) [56].
Scheme 2
Scheme 2
Preparation of N-phenylquinoneimine 1 [60].
Scheme 3
Scheme 3
Reactions of N-Phenylquinoneimine leading to structural complexity [21].
Scheme 4
Scheme 4
Nucleophilic attack via 1,2-addition to the ketone or the imine.
Scheme 5
Scheme 5
Nucleophilic attack via 1,4-conjugate addition.
Scheme 6
Scheme 6
Addition of aliphatic amine to NPQ [21,66].
Scheme 7
Scheme 7
The reaction mechanism of the 1,4-conjugate addition of aromatic amines to the α,β-unsaturated ketone and α,β-unsaturated imine of NPQ [21,76].
Scheme 8
Scheme 8
Reaction of aromatic amines with NPQ and subsequent oxidation to phenazinones [76].
Scheme 9
Scheme 9
Reactions of thiols with NPQ [78].
Scheme 10
Scheme 10
Alternative mode of addition of thiols to NPQ.
Scheme 11
Scheme 11
Addition of sodium arenesulfinates to NPQ derivatives [80].
Figure 7
Figure 7
Some useful sulfone-containing compounds.
Scheme 12
Scheme 12
Reaction of HBr with NPQ [84].
Scheme 13
Scheme 13
Addition of hydrochloric acid to NPQ [85].
Scheme 14
Scheme 14
Reaction of NPQ with dimedone [86].
Scheme 15
Scheme 15
The reaction of NPQ with organometallic reagents [87].
Scheme 16
Scheme 16
Oxidation of NPQ.
Scheme 17
Scheme 17
Cycloaddition reaction of NPQ with diphenylketene.
Scheme 18
Scheme 18
Suzuki reaction of compound 36 with arylboronic acids.
Scheme 19
Scheme 19
Stille reaction of compound 36 with arylstannanes [21,92].
Scheme 20
Scheme 20
Reaction of 3-bromo NPQ with isopropylmagnesium chloride [21,91].
Scheme 21
Scheme 21
Reaction of 3-bromoNPQ with aniline derivatives [21].
See this image and copyright information in PMC

References

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