How five different isoforms of N,N,N-Tris(tert-butoxycarbonyl)-L-arginine whose reactivity in esterification reactions was subsequently investigated were obtained

Description

L-arginine, nowadays, is more and more used to functionalize scaffolds for producing delivery systems with high transfection activity and low toxicity. For these purposes it is better to be protected to basic nitrogen atoms. A well known protective residue is tert-butoxycarbonyl group (BOC) and three protocols of BOC-protection selected by us assured that the widely cited (E)-αN,ωN,ω'N-tris(tert-butyloxycarbonyl)-L-arginine would be the only product obtainable. Surprisingly we achieved also other four isoforms (Figure 1) [1]. With the first tested procedure [2] αN,ωN,ω'N-Tris(tert-butyloxycarbonyl)-L-arginine was never obtained. The second one [3] provided the goal compound but in mixture with the Z rotamer while the third protocol [4] 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 investigations about the behavior of each one of the isoforms obtained in esterification reactions, whose results have been described in details in another work by us presented in this context, shown that their reactivity depends on their structure. With this work we reported a thorough description of this unexpected results and the meticulous NMR investigation performed with particular care for double bonds geometry and position which confirmed the structures. References: 1. S. Alfei, S. Castellaro, Res. Chem. Intermediat. 44, 1811 (2018) DOI: 10.1007/s11164-017-3199-6. 2. H. Konno, K. Kubo, H. Makabe, E. Toshiro, N. Hinoda, K. Nosakaa, K: Akaji, Tetrahedron 63, 9502 (2007) doi:10.1016/j.tet.2007.06.082.3. J. Izdebski, T. Gers, D. Kunce, P. Markovsky, J. Pept. Sci. 11, 60 (2005) doi: 10.1002/psc.585.4. M. A. Jones, A. D. Hislop, J. S. Snaith, Org. Biomol. Chem. 4, 3769 (2006) doi: 10.1039/b611170j

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