ESTONIAN ACADEMY
PUBLISHERS
eesti teaduste
akadeemia kirjastus
PUBLISHED
SINCE 1952
 
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proceedings
of the estonian academy of sciences
ISSN 1736-7530 (Electronic)
ISSN 1736-6046 (Print)
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Synthesis of the Fmoc-aza-Arg(Boc)2 precursor via hydrazine alkylation; pp. 438–443

Full article in PDF format | doi: 10.3176/proc.2014.4.09

Authors
Anton Mastitski, Ksenija Kisseljova, Jaak Järv

Abstract

The aza-arginine precursor Fmoc-aza-Arg(Boc)2 was synthesized starting from mono-protected hydrazines via an aza-ornithine precursor. This reaction path is shorter and more efficient than the reductive alkylation reaction.


References

  1. Zega, A. Azapeptides as pharmacological agents. Curr. Med. Chem., 2005, 12, 589–597.
http://dx.doi.org/10.2174/0929867310504050589

  2. Proulx, C., Sabatino, D., Hopewell, R., Spiegel, J., Garcia Ramos, Y., and Lubell, W. D. Azapeptides and their therapeutic potential. Fut. Med. Chem., 2011, 3, 1139–1164.
http://dx.doi.org/10.4155/fmc.11.74

  3. Quibell, M., Turnell, W. G., and Johnson, T. Synthesis of azapeptides by the Fmoc/tert-butyl/polyamide technique. J. Chem. Soc., Perkin Trans. 1, 1993, 2843–2849.
http://dx.doi.org/10.1039/p19930002843

  4. Busnel, O., Bi, L., Dali, H., Cheguillaume, A., Chevance, S., Bondon, A., Muller, S., and Baudy-Floc’h, M. Solid-phase synthesis of “mixed” peptidomimetics using Fmoc-protected Aza-β3-amino acids and α-amino acids. J. Org. Chem., 2005, 70, 10701–10708.
http://dx.doi.org/10.1021/jo051585o

  5. Boeglin, D. and Lubell, W. D. Aza-amino acid scanning of secondary structure suited for solid-phase peptide synthesis with Fmoc chemistry and aza-amino acids with heteroatomic side chains. J. Comb. Chem., 2005, 7(6), 864–878.
http://dx.doi.org/10.1021/cc050043h

  6. Spiegel, J., Mas-Moruno, C., Kessler, H., and Lubell, W. D. Cyclic aza-peptide integrin ligand synthesis and biological activity. J. Org. Chem., 2012, 77, 5271–5278.
http://dx.doi.org/10.1021/jo300311q

  7. Lee, J. and Bogyo, M. Development of near-infrared fluorophore (NIRF)-labeled activity-based probes for in vivo imaging of legumain. ACS Chem. Biol., 2010, 5, 233–243.
http://dx.doi.org/10.1021/cb900232a

  8. Busnel, O. and Baudy-Floc’h, M. Preparation of new mono­mers aza-β3-aminoacids for solid-phase syntheses of aza-β3-peptides. Tetrahedron Lett., 2007, 48, 5767–5770.
http://dx.doi.org/10.1016/j.tetlet.2007.06.082

  9. Bondebjerg, J., Fuglsang, H., Valeur, K. R., Kaznel­son, D. W., Hansen, J. A., Pedersen, R. O. et al. Novel semicarbazide-derived inhibitors of human dipeptidyl peptidase I (hDPPI). Bioorg. Med. Chem., 2005, 13(14), 4408–4424.
http://dx.doi.org/10.1016/j.bmc.2005.04.048

10. Peifer, M., Giacomo, F. D., Schandl, M., and Vasella, A. Oligonucleotide analogues with integrated bases and backbone hydrazide- and amide-linked analogues. 1. Design and synthesis of monomeric building blocks. Helv. Chim. Acta, 2009, 92(6), 1134–1166.
http://dx.doi.org/10.1002/hlca.200900047

11. Bernatowicz, M. S., Wu, Y., and Matsueda, G. R. Urethane protected derivatives of 1-guanylpyrazole for the mild and efficient preparation of guanidines. Tetrahedron Lett., 1993, 34, 3389–3392.
http://dx.doi.org/10.1016/S0040-4039(00)79163-5

12. Freeman, N. S., Tal-Gan, Y., Klein, S., Levitzki, A., and Gilon, C. Microwave-assisted solid-phase aza-peptide synthesis: aza scan of a PKB/Akt inhibitor using aza-arginine and aza-proline precursors. J. Org. Chem., 2011, 76, 3078–3085.
http://dx.doi.org/10.1021/jo102422x

13. Carpino, L. A. and Han, G. Y. The 9-fluorenylmethoxy­carbonyl amino-protecting group. J. Org. Chem., 1972, 37, 3404–3409.
http://dx.doi.org/10.1021/jo00795a005

14. Rabjohn, N. The synthesis and reactions of disazodi­carboxylates. J. Am. Chem. Soc., 1948, 70, 1181–1183.
http://dx.doi.org/10.1021/ja01183a089

15. Hofmann, K., Lindenmann, A., Magee, M. Z., and Khan, N. H. Studies on polypeptides. III.1 Novel routes to α-amino acid and polypeptide hydrazides. J. Am. Chem. Soc., 1952, 74, 470–476.
http://dx.doi.org/10.1021/ja01122a057

16. Levy, D. E., Wang, D.-X., Lu, Q., Chen, Z., Peru­mattam, J., Xu, Y. et al. Aryl–indolyl maleimides as inhibitors of CaMKIId. Part 1: SAR of the aryl region. Bioorg. Med. Chem. Lett., 2008, 18, 2390–2394.
http://dx.doi.org/10.1016/j.bmcl.2008.02.058

17. Chunhui, D., Narayanam, J. M. R., and Stephen­son, C. R. J. Visible-light-mediated conversion of alcohols to halides. Nature Chemistry, 2011, 3, 140–145.
http://dx.doi.org/10.1038/nchem.949

18. Gellerman, G., Elgavi, A., Salitra, Y., and Kramer, M. Facile synthesis of orthogonally protected amino acid building blocks for combinatorial N-backbone cyclic peptide chemistry. J. Pept. Res., 2001, 57, 277–291.
http://dx.doi.org/10.1046/j.1397-002x.2000.0780.x

19. Hansen, T. K. Synthesis of azapeptides from hindered amines leading to novel growth hormone secretagogues. Tetrahedron Lett., 1999, 40, 9119–9120.
http://dx.doi.org/10.1016/S0040-4039(99)01888-2

20. Feichtinger, K., Zapf, C., Sings, H. L., and Goodman, M. Diprotected triflylguanidines: a new class of guanidinylation reagents. J. Org. Chem., 1998, 63, 3804–3805.
http://dx.doi.org/10.1021/jo980425s


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