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. 2025 Jan 22;10(4):3622-3626.
doi: 10.1021/acsomega.4c08497. eCollection 2025 Feb 4.

Short and High-Yielding Synthesis of a Minimalist Diazirine-Alkyne Photo-Cross-Linker and Photoaffinity Labeling Derivatives

Dare E George  1   2 , Miracle O Olatunde  2 , Jetze J Tepe  2
Affiliations

Short and High-Yielding Synthesis of a Minimalist Diazirine-Alkyne Photo-Cross-Linker and Photoaffinity Labeling Derivatives

Dare E George et al. ACS Omega. .

Abstract

Minimalist photo-cross-linker 1 and its derivatives are extensively utilized in photoaffinity labeling studies. However, obtaining compound 1 in high yield has traditionally required a lengthy synthetic process. In this paper, we present a concise and efficient method to synthesize 1 in just four steps, leveraging the "Normant reagent" as a pivotal component in our strategy. Additionally, we extended our synthetic approach to generate new derivatives of the fully functionalized diazirine tag, providing versatile handles for coupling with other small molecules. This work provides a quick and high-yielding approach to access photo-cross-linker 1 compared to previously reported approaches.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Structure of minimalist alkyne diazirine 1 and derivatives 2 and 3.
Figure 2
Figure 2
Previous approaches to access minimalist diazirine photo-cross-linker 1 by Li et al. and Parker et al. and our approach shown in this work.
Scheme 1
Scheme 1. Synthesis of Diazirine Photo-Cross-Linker 1
Scheme 2
Scheme 2. Synthesis of Alkyl Iodide 9 and Amine 11 Derivatives
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