Amphiphilic analogues of peptidoamines with per¯uorinated side chains Synthesis and preliminary investigations of their surfactant and complexing abilities Sedat Cosgun a , Mehmet O È zer a , Faouzia Hamdoune b , Christine Gerardin a , Sylvie Thiebaut a , Bernard Henry a , Jacques Amos a , Ludwig Rodehu Èser a , Claude Selve a,* a Faculte  des Sciences, Laboratoire de Chimie Physique Organique et Colloõ Èdale, Universite  Henri Poincare Â, Nancy I, UMR CNRS-UHP No. 7565, BP 239, F-54506 Vandoeuvre les Nancy Cedex, France b De Âpartement de Chimie, Faculte  des Sciences et Techniques, Universite  Abdelmalek Essaadi, BP 416, Tanger, Morocco Received 3 April 2000; accepted 5 May 2000 Abstract A new synthetic pathway for preparing per¯uorinated b-alanines is described. 2-Per¯uoroalkyl-ethanols are oxidized, dehydro- ¯uorinated, substituted with an azide group and ®nally hydrogenated with excellent yields. The C-per¯uoroalkylated b-alanines obtained in this way are subsequently used as hydrophobic moieties for the synthesis of amphiphilic lipo-peptides and lipo-peptidoamines. The choice of the peptidoamine structure is justi®ed by the anti-oxidative and complexing properties of natural analogues such as carcinine and carnosine. Measurements of the surface tension of aqueous solutions of the compounds synthesized reveal their surfactant properties. Potentiometric and spectroscopic investigations give evidence for their good ability to complex copper(II) ions in solution. # 2001 Elsevier Science B.V. All rights reserved. Keywords: Per¯uoroalkyl-b-alanine; Per¯uoroalkyl-peptidoamine; Surfactants; Critical concentration; Complexation 1. Introduction Many biological applications use ¯uorinated organic compounds and chemical research in this ®eld gives rise to numerous publications [1,2]. The surfactants pertaining to this family are of particular interest for the preparation of ¯uids capable to transport respiratory gases [3±5]. However, the high concentrations of oxygen supplied by these solu- tions may lead to the formation of toxic derivatives (per- oxides, free radicals) [6] in amounts such that the natural defense mechanisms of the organism can no longer cope with them [7]. We have, therefore, attempted to solve this dif®culty by synthesizing molecules bearing a per¯uorinated hydropho- bic chain which exhibit simultaneously surfactant and potentially anti-oxidative properties. Among the bio-pro- tecting substances certain metal complexes of pseudopep- tides of the peptidoamine type are known for their anti-oxidative action [8,9]. We have shown previously [10] that lipo-oligopeptide structures are surface active. The peptidoamines containing an imidazol moiety stem- ming from histidine or histamine structures [11±13], in particular carcinine [14] and carnosine [15,16] seemed to us the most promising. The structures of these two dipep- tides are shown in Scheme 1. Both contain the b-alanine moiety linked via a peptide bond either to histidine (in carnosine) or to histamine (in carcinine). We have described ef®cient syntheses of b- per¯uoroalkyl-b-alanines previously [17]. These com- pounds may be used as hydrophobic junction modules in modular synthetic pathways [18,19]. In this paper we describe the preparation of carnosine and carcinine analo- gues starting from b-per¯uoroalkyl-b-alanines, and the investigation of some of their physico-chemical properties. The new compounds are surfactants and good ligands for divalent cations such as copper(II). Journal of Fluorine Chemistry 107 (2001) 375±386 * Corresponding author. Tel.: 33-3-83-91-23-60; fax: 33-3-83-91-25-32. E-mail address: claude.selve@lesoc.uhp-nancy.fr (C. Selve). 0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved. PII:S0022-1139(00)00381-X