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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Synthesis and Characterization of FlAib, a CompletelyRigidified Benzophenone Containing α-Amino AcidKaren Wright 1 , Antonio Blanco Alvarez 1 , Marco Crisma 2 ,Alessandro Moretto 2 , Fernando Formaggio 2 , and Claudio Toniolo 21 ILV, UMR CNRS 8180, University of Versailles, Versailles, 78035, France; 2 ICB, PadovaUnit, CNR, Department of Chemistry, University of Padova, Padova, 35131, ItalyIntroductionPhotoreactive amino acids with benzophenone side chains, such as the widely used Bpa[3-(4-benzoylphenyl)alanine] (Figure 1) [1], have been used as photoprobes for thecovalent modification of enzymes and receptors in protein-mapping studies. However,results of photocross-linking experiments need to take into account the high flexibility ofthe Bpa side chain [2]. Since incorporation of a cyclic structure into the amino acid sidechain reduces flexibility, we have designed and synthesized an extremely highlyconstrained fluorenone-containing amino acid, FlAib (2-amino-1,2,3,6-tetrahydro-6-oxocyclopenta[c]fluorene-2-carboxylic acid) (Figure 1), belonging to the sub-class of theC i α ↔C i α cyclized, C α -tetrasubstituted α-amino acids, which are known to induce β-turnand helix formation in peptides [3]. A more flexible residue of this family, BpAib (2-amino-5-benzoyl-2,3-dihydro-1H-indene-2-carboxylic acid) (Figure 1), was alreadyprepared and studied by our groups [4].Fig. 1. Chemical structures of Bpa, BpAib, and FlAib.Fig. 2. Scheme followed for the resolution of the diastereomeric mixture of FlAib. (i)Bz 2 O, MeCN; rt. (ii) NaOH, THF/MeOH/H 2 O; 60°C. (iii) H-(S)-Phe-NHChex, HATU,DIEA; THF; rt. (iv) 10 M HCl, dioxane; 100°C. (v) SOCl 2 ; MeOH; rt.46