The Synthesis of Enantiopure α-Fluoro and α,α-Difluoro-β3-Arginine Derivatives

Taryn L. March; Jamie A. Freemont; Geoff Dumsday; Martin R. Johnston; Peter J. Duggan

doi:10.1071/CH13590

RESEARCH ARTICLE

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The Synthesis of Enantiopure α-Fluoro and α,α-Difluoro-β³-Arginine Derivatives

Taryn L. March ^A , Jamie A. Freemont ^B , Geoff Dumsday ^B , Martin R. Johnston ^A and Peter J. Duggan ^A ^B ^C

+ Author Affiliations

- Author Affiliations

^A School of Chemical and Physical Sciences, Flinders University, Adelaide, SA 5042, Australia.

^B CSIRO Materials Science and Engineering, Bag 10, Clayton South, Vic. 3169, Australia.

^C Corresponding author. Email: peter.duggan@csiro.au

Australian Journal of Chemistry 67(7) 997-1004 https://doi.org/10.1071/CH13590
Submitted: 31 October 2013 Accepted: 3 December 2013 Published: 20 January 2014

Abstract

The synthesis of a set of monofluorinated, difluorinated, and non-fluorinated N-acetylated-β³-arginine esters, potential inhibitors of trypsin-like proteases, is described. Elaboration to the target compounds from previously reported enantiopure precursors derived from 3-hydroxypropanal involved 6–7 steps and was achieved in 48–65 % overall yield. The α,α-difluoro-β³-arginine derivative was found to be particularly prone to hydrolysis. Three β³-arginine derivatives were tested for their ability to inhibit trypsin, the α,α-difluoro compound being assayed in the form of a carboxylate zwitterion.

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The Synthesis of Enantiopure α-Fluoro and α,α-Difluoro-β3-Arginine Derivatives

Abstract

References

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The Synthesis of Enantiopure α-Fluoro and α,α-Difluoro-β³-Arginine Derivatives