Synthesis of Succinimidoalkylbenzaldehyde Analogues: Potential Bifunctional Linkers for Bioconjugation

Ian T. Crosby; Geoffrey A. Pietersz; Justin A. Ripper

doi:10.1071/CH07404

RESEARCH ARTICLE

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Synthesis of Succinimidoalkylbenzaldehyde Analogues: Potential Bifunctional Linkers for Bioconjugation

Ian T. Crosby ^A ^D , Geoffrey A. Pietersz ^B and Justin A. Ripper ^A ^C

+ Author Affiliations

- Author Affiliations

^A Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University (Parkville), 381 Royal Parade, Parkville, VIC 3052, Australia.

^B MacFarlane Burnet Institute, Austin Hospital, Studley Rd, Heidelberg, VIC 3084, Australia.

^C Current address: Bionomics Limited, 31 Dalgleish Street, Thebarton, SA 5031, Australia.

^D Corresponding author. Email: ian.crosby@vcp.monash.edu.au

Australian Journal of Chemistry 61(2) 138-143 https://doi.org/10.1071/CH07404
Submitted: 21 November 2007 Accepted: 14 January 2008 Published: 11 February 2008

Abstract

A series of novel 4-substituted benzaldehydes containing a succinimide moiety were synthesized as potential bifunctional linkers for the purpose of binding therapeutic drugs to antibodies raised against cancer cells. These potential benzaldehyde linkers varied in the nature of the para functionality so as to provide a range of potential acid labilities. Synthesis of the linkers involved a Williamson ether formation to make the ether linker 1, a Sonagoshira palladium-catalyzed coupling to synthesize the skeleton of the alkyl linker 2, and formation of an amide bond directly from a methyl ester gave the 4-substituted amide linker 3. As an example of the type of acetal that can be produced using these linkers, uridine was used as an analogue of the cytotoxic compound 5-fluorouridine to give the cyclic acetals 19–21.

References

Synthesis of Succinimidoalkylbenzaldehyde Analogues: Potential Bifunctional Linkers for Bioconjugation

Abstract

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