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Synlett 2008(7): 958-962  
DOI: 10.1055/s-2008-1072653
LETTER
© Georg Thieme Verlag Stuttgart · New York

The Influence of Fluoroalkyl-Group Electronegativity on Stereocontrol in the Synthesis of Ψ[CH(RF)NH]Gly Peptides

Serena Bigottia, Alessandro Volonterio*a, Matteo Zanda*b
a Dipartimento di Chimica, Materiali ed Ingegneria Chimica ‘G. Natta’ del Politecnico di Milano, via Mancinelli 7, 20131 Milano, Italy
e-Mail: alessandro.volonterio@polimi.it;
b C.N.R-Istituto di Chimica del Riconoscimento Molecolare, Sezione ‘A. Quilico’, via Mancinelli 7, 20131 Milano, Italy
Fax: +39(02)23993080; e-Mail: matteo.zanda@polimi.it;
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Publikationsverlauf

Received 19 January 2008
Publikationsdatum:
28. März 2008 (online)

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Abstract

New peptidomimetics featuring CH(RF)NH units, having different degree of fluorination, as peptide-bond surrogates have been synthesized. The key step in the synthesis consists of a stereoselective aza-Michael addition of chiral α-amino acid esters to β-fluoroalkyl-α-nitroethenes. The diastereoselection of the process was influenced by the electronegativity, rather than by the steric bulk, of the fluorinated residue RF in β-position of the nitroalkene acceptors. Replacement of a single F atom of RF by a hydrogen or methyl group brings about a dramatic drop of stereocontrol, whereas Br, Cl, and CF3, albeit bulkier than F, provide poorer results in terms of stereocontrol.

Key words

peptidomimetics - fluorine - electronegativity - peptide bond surrogate - fluoroalkyl

    References and Notes

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12

The stereochemistry of the diastereoisomers was assessed by X-ray diffraction of a Michael adduct and on the basis of their spectroscopic and analytical features. Full details will be given in a full paper.