L-arginine is often used to decorate lipid matrices and polymer or dendrimer scaffolds, to obtain synthetic vectors for gene therapy or drug delivery with increased transfection activity and reduced toxicity. For this purpose, its basic nitrogen atoms need protection for example with tert-butoxycarbonyl group. In a previous study, following three reported protocols which assured the achievement of the widely described (E)-αN,ωN,ω’N-Tris(tert-butoxycarbonyl)-L-arginine as pure isoform [1,2,3], further four isoforms were obtained: the rotamer Z, αN,δN,ωN- and αN,δN,ω’N-Tris(tert-butoxycarbonyl)-L-arginine and the unknown symmetric compound not affected by geometric isomerism, αN,ωN,ω’N-Tris(tert-butoxycarbonyl)-L-arginine [4]. Aiming at demonstrating the importance of the position of the protective groups, even if transients, we performed studies about the reactivity of any isoform in esterification reactions of a 1,3-propandiol derivative taken as model molecule. Then in this communication the obtained results were reported and discussed. We have shown that the structure of the isoform and BOC location influence its reactivity and have highlighted how much to prepare an isoform rather than another may have more or less advantageous repercussions on future reactions (Figure 1). Furthermore we described the preparation, isolation and characterization of two unreported first generation arginine dendrons achieved during the investigations and considered by us appealing fragments for decorating the periphery of polyesters or polyamidoamine dendrimer scaffolds for the obtainment of new synthetic polycationic vectors for gene transfection or drug delivery (Figure 2). Finally the isolation and spectral characterization of three unreported compounds (9a, 11 E/Z and 16) were also provided. 1. H. Konno, K. Kubo, H. Makabe, E. Toshiro, N. Hinoda, K. Nosakaa, K. Akaji, Tetrahedron 63, 9502 (2007) doi:10.1016/j.tet.2007.06.082. 2. J. Izdebski, T. Gers, D. Kunce, P. Markovsky, J. Pept. Sci. 11, 60 (2005) doi: 10.1002/psc.585. 3. M. A. Jones, A. D. Hislop, J. S. Snaith, Org. Biomol. Chem. 4, 3769 (2006) doi: 10.1039/b611170j. 4. S. Alfei, S. Castellaro, Res. Chem. Intermediat. 44, 1811 (2018) DOI: 10.1007/s11164-017-3199-6.

An investigation about the reactivity of five isoforms of N, N, N-Tris(tert-butoxycarbonyl)-L-arginine in esterification reactions of a 1, 3-propandiol derivative

Silvana Alfei;Sara Castellaro;Gaby Brice Taptue
2018

Abstract

L-arginine is often used to decorate lipid matrices and polymer or dendrimer scaffolds, to obtain synthetic vectors for gene therapy or drug delivery with increased transfection activity and reduced toxicity. For this purpose, its basic nitrogen atoms need protection for example with tert-butoxycarbonyl group. In a previous study, following three reported protocols which assured the achievement of the widely described (E)-αN,ωN,ω’N-Tris(tert-butoxycarbonyl)-L-arginine as pure isoform [1,2,3], further four isoforms were obtained: the rotamer Z, αN,δN,ωN- and αN,δN,ω’N-Tris(tert-butoxycarbonyl)-L-arginine and the unknown symmetric compound not affected by geometric isomerism, αN,ωN,ω’N-Tris(tert-butoxycarbonyl)-L-arginine [4]. Aiming at demonstrating the importance of the position of the protective groups, even if transients, we performed studies about the reactivity of any isoform in esterification reactions of a 1,3-propandiol derivative taken as model molecule. Then in this communication the obtained results were reported and discussed. We have shown that the structure of the isoform and BOC location influence its reactivity and have highlighted how much to prepare an isoform rather than another may have more or less advantageous repercussions on future reactions (Figure 1). Furthermore we described the preparation, isolation and characterization of two unreported first generation arginine dendrons achieved during the investigations and considered by us appealing fragments for decorating the periphery of polyesters or polyamidoamine dendrimer scaffolds for the obtainment of new synthetic polycationic vectors for gene transfection or drug delivery (Figure 2). Finally the isolation and spectral characterization of three unreported compounds (9a, 11 E/Z and 16) were also provided. 1. H. Konno, K. Kubo, H. Makabe, E. Toshiro, N. Hinoda, K. Nosakaa, K. Akaji, Tetrahedron 63, 9502 (2007) doi:10.1016/j.tet.2007.06.082. 2. J. Izdebski, T. Gers, D. Kunce, P. Markovsky, J. Pept. Sci. 11, 60 (2005) doi: 10.1002/psc.585. 3. M. A. Jones, A. D. Hislop, J. S. Snaith, Org. Biomol. Chem. 4, 3769 (2006) doi: 10.1039/b611170j. 4. S. Alfei, S. Castellaro, Res. Chem. Intermediat. 44, 1811 (2018) DOI: 10.1007/s11164-017-3199-6.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/927755
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