L-arginine is often covalently linked to delivery systems for increasing their transfection activity and reducing toxicity and its basic nitrogen atoms need protection for example with tert-butoxycarbonyl group. Following three reported protocols which assured the goal of obtaining the widely cited αN,ωN,ω’N-tris(tert-butyloxycarbonyl)-L-arginine, surprisingly we achieved also other four isoforms (Figure 1). With the first selected procedure [1] αN,ωN,ω’N-Tris(tert-butyloxycarbonyl)-L-arginine was never obtained. The second one [2] provided the desired compound but as a mixture of geometric isomers E/Z while the third [3] protocol led to a single very pure isoform in high yield but with an unreported symmetrical structure. Since BOC protection is transient this discovery would seem of poor interest but results obtained from following investigations about the behavior of each one of the isoforms obtained in the esterification reactions of our interest shown that their reactivity depends on their structure. With this work we reported a detailed description of this unexpected results and the NMR investigation performed with particular care for double bonds geometry and position which confirmed the structures. [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
N,N,N-Tris(tert-butoxycarbonyl)-L-arginine: five isoforms whose obtainment depends on procedure and a scrupulous NMR confirmation of their structures.
Alfei S.;Castellaro S.
2018-01-01
Abstract
L-arginine is often covalently linked to delivery systems for increasing their transfection activity and reducing toxicity and its basic nitrogen atoms need protection for example with tert-butoxycarbonyl group. Following three reported protocols which assured the goal of obtaining the widely cited αN,ωN,ω’N-tris(tert-butyloxycarbonyl)-L-arginine, surprisingly we achieved also other four isoforms (Figure 1). With the first selected procedure [1] αN,ωN,ω’N-Tris(tert-butyloxycarbonyl)-L-arginine was never obtained. The second one [2] provided the desired compound but as a mixture of geometric isomers E/Z while the third [3] protocol led to a single very pure isoform in high yield but with an unreported symmetrical structure. Since BOC protection is transient this discovery would seem of poor interest but results obtained from following investigations about the behavior of each one of the isoforms obtained in the esterification reactions of our interest shown that their reactivity depends on their structure. With this work we reported a detailed description of this unexpected results and the NMR investigation performed with particular care for double bonds geometry and position which confirmed the structures. [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
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