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. 2019 Apr 4;24(7):1327.
doi: 10.3390/molecules24071327.

MCR Scaffolds Get Hotter with 18F-Labeling

Tryfon Zarganes-Tzitzikas  1 , Gonçalo S Clemente  2 , Philip H Elsinga  3 , Alexander Dömling  4
Affiliations

MCR Scaffolds Get Hotter with 18F-Labeling

Tryfon Zarganes-Tzitzikas et al. Molecules. .

Abstract

Imaging techniques, such as positron emission tomography (PET), represent great progress in the clinical development of drugs and diagnostics. However, the efficient and timely synthesis of appropriately labeled compounds is a largely unsolved problem. Numerous small drug-like molecules with high structural diversity can be synthesized via convergent multicomponent reactions (MCRs). The combination of PET labeling with MCR synthesis of biologically active compounds can greatly simplify radioanalytical and imaging-based analysis. In a proof-of-concept study, we optimized robust on-site radiolabeling conditions that were subsequently applied to several structurally different drug-like MCR scaffolds (e.g., arenes, β-lactam, tetrazole, and oxazole). These labeled scaffolds were synthesized via pinacol-derived aryl boronic esters (arylBPin) by copper-mediated oxidative 18F-fluorination with radiochemical conversions (RCCs) from 15% to 76%.

Keywords: boronic pinacol esters; fluor-18; multicomponent reactions; positron emission tomography; radiochemistry.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Current and potential multicomponent reaction (MCR) approaches for the generation of scaffold diversity.
Scheme 1
Scheme 1
Copper-mediated oxidative 18F-fluorination of aryl boronic esters (arylBPin).
Figure 2
Figure 2
Impact of the Cu catalyst and precursor in the radiochemical conversion (RCC) of 4-[18F]fluorobenzaldehyde [18F]1 (assessed by radio-TLC).
Scheme 2
Scheme 2
Cu-mediated late-stage 18F-fluorination of simple arenes.
Scheme 3
Scheme 3
General MCR synthesis and 18F-fluorination of β-lactam scaffold.
Scheme 4
Scheme 4
General MCR synthesis and 18F-fluorination of tetrazole scaffold.
Scheme 5
Scheme 5
General synthesis and 18F-fluorination of oxazole scaffold.
Scheme 6
Scheme 6
General MCR synthesis and 18F-fluorination of α-acyloxy carboxamides.
See this image and copyright information in PMC

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