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Synthesis 2010(11): 1845-1859  
DOI: 10.1055/s-0029-1218743
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart ˙ New York

Fluorinated β²- and β³-Amino Acids: Synthesis and Inhibition of α-Chymotrypsin

Victoria Peddiea,b,1, Markus Pietscha,1, Karen M. Bromfieldc,2, Robert N. Piked, Peter J. Duggane, Andrew D. Abell*a
a School of Chemistry & Physics, The University of Adelaide, Adelaide, South Australia 5005, Australia
Fax: +61(8)83034358; e-Mail: andrew.abell@adelaide.edu.au;
b Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand
c Centre for Green Chemistry, Monash University, Clayton, Victoria 3800, Australia
d Department of Biochemistry & Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
e CSIRO Molecular and Health Technologies, Bag 10, Clayton South, Victoria 3169, Australia
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Publication History

Received 10 March 2010
Publication Date:
15 April 2010 (online)

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Abstract

The synthesis of a series of α-fluorinated β²- and β³-amino acid derivatives is described. Stereoselective fluorination at the α-carbon of the β³-amino acids was achieved by deprotonation with lithium diisopropylamide followed by treatment with N-fluorobenzenesulfonimide. Fluorination of β²-amino acids employed the chiral auxiliary (4R)-4-benzyl-2-oxazolidinone. The α-fluorinated amino acids and their non-fluorinated precursors were found to competitively inhibit α-chymotrypsin.

Key words

β-amino acids - fluorination - crystal structure - α-chymotrypsin - inhibitor

1

These authors contributed equally to this work.

2

New address: K. M. Bromfield, Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge CB2 1EW, UK.