A Facile and Convenient Synthesis of Boc-Protected 5-Carboxyspermine

Author(s): Jong-Soo Choi, Jae-Won Park, Bieong-Kil Kim, Kyung-Oh Doh, Young-Bae Seu*.

Journal Name: Letters in Organic Chemistry

Volume 16 , Issue 8 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Gene therapy is a powerful technology for treating incurable and hereditary disease in humans. In the recent years, a lot of studies have been done on the development of DNA carriers. Nonviral vectors, like liposomes, polymers, and micelles, has become common vehicles due to their safety. The key compound of DOGS, DOSPA and DOSPER is the 5-carboxyspermine which formed the poly amine head-group and carries four positive charges. In general, multivalent head-group shows more transfection efficiency than monovalent analogues. In this paper, the efficient and simple synthesis of Boc-protected 5-carboxyspermine is described. Boc-protected polyamines were synthesized from (S)- 2,5-diaminopentanoic acid monohydrochloride (L-ornithine) monohydrochloride through both cyanoethylation and direct catalytic reduction of nitriles with the combination of nickel (II) chloride, sodium borohydride and di-tert-butyl decarbonate (BOC2O) in a one-pot two-reaction.

Keywords: Boc protection, 5-carboxyspermine, cationic lipids, cyanoethylation, nitrile reduction, polyamines.

[1]
Anderson, W.F. Nature, 1998, 392(6679)(Suppl.), 25-30.
[2]
Xu, Y.; Li, A.; Wu, G. Liang. C. Curr. Gene Ther., 2017, 17, 43-49.
[3]
Islam, M.A.; Park, T.E.; Singh, B.; Maharjan, S.; Firdous, J.; Cho, M.H.; Kang, S.K.; Yun, C.H.; Choi, Y.J.; Cho, C.S. J. Control. Release, 2014, 193, 74-89.
[4]
Junquera, E.; Aicart, E. Adv. Colloid. Interfac., 2015, 233, 161-175.
[5]
Thomas, C.E.; Ehrhardt, A.; Kay, M.A. Nat. Rev. Genet., 2003, 4(5), 346-358.
[6]
Pandey, A.P.; Sawant, K.K. Mater. Sci. Eng. C, 2016, 68, 904-918.
[7]
Yingyongnarongkul, B.E.; Howarth, M.; Elliott, T.; Bradley, M. Chemistry, 2004, 10(2), 463-473.
[8]
Behr, J.P.; Demeneix, B.; Loeffler, J.P.; Perez-Mutul, J. P. Natl. Acad. Sci. USA, 1989, 86(18), 6982-6986.
[9]
Morille, M.; Passirani, C.; Vonarbourg, A. Biomaterials, 2008, 29, 3477-3496.
[10]
Lavigne, C.; Thierry, A.R. Biochimie, 2007, 89, 1245-1251.
[11]
Lewis, J.G.; Lin, K.Y.; Kothavale, A.; Flanagan, W.M.; Matteucci, M.D.; DePrince, R.B.; Mook, R.A.; Hendren, R.W.; Wagner, R.W. Proc. Natl. Acad. Sci. USA, 1996, 93(8), 3176-3181.
[12]
Zuris, J.A.; Thompson, D.B.; Shu, Y.; Guilinger, J.P.; Bessen, J.L.; Hu, J.H.; Maeder, M.L.; Joung, J.K.; Chen, Z.Y.; Liu, D.R. Nat. Biotechnol., 2015, 33, 73-80.
[13]
Ran, F.A.; Cong, L.; Yan, W.X.; Scott, D.A.; Gootenberg, J.S.; Kriz, A.J.; Zetsche, B.; Shalem, O.; Wu, X.; Makarova, K.S.; Koonin, E.V.; Sharp, P.A.; Zhang, F. Nature, 2015, 520, 186-191.
[14]
Buchberger, B.; Fernhol, E.; Bantle, E.; Weigert, M.; Borowski, E. Biochemica, 1996, 2, 7-10.
[15]
Urbiola, K.; Garcia, L.; Zalba, S.; Garrido, M.J.; Tros de Ilarduya, C. Eur. J. Pharm. Biopharm., 2013, 83, 358-363.
[16]
Ronsin, G.; Perrin, C.; Guedat, P.; Kremer, A.; Camilleri, P.; Kirby, A.J. Chem. Commun., 2001, 21, 2234-2235.
[17]
Shirazi, R.S.; Ewert, K.K.; Leal, C.; Majzoub, R.N.; Bouxsein, N.F.; Safinya, C.R. Biochim. Biophys. Acta, 2011, 1808, 2156-2166.
[18]
Hou, M.H.; Lin, S.B.; Yuann, J.M.; Lin, W.C.; Wang, A.H.; Kan, L. Nucleic Acids Res., 2001, 29(24), 5121-5128.
[19]
Winklhofer, K.F.; Tatzelt, J. Biol. Chem., 2000, 381, 463-469.
[20]
David, S.A.; Silverstein, R.; Amura, C.R.; Kielian, T.; Morrison, D.C. Antimicrob. Agents. Ch., 1999, 43(4), 912-919.
[21]
Behr, J.P. J. Chem. Soc. Chem. Commun., 1989, 2, 101-103.
[22]
Huber, M.; Pelletier, J.G.; Torossian, K.; Dionne, P.; Gamache, I.; Charest Gaudreault, R.; Audette, M.; Poulin, R. J. Biol. Chem., 1996, 271(44), 27556-27563.
[23]
Cao, H. Probe oxidative damage in DNA charge transfer process, PhD Thesis, The Georgia Institute of Technology, December. 2004.
[24]
Khurana, J.M.; Kukreja, G. Syn. Commun., 2002, 32(8), 1265-1269.
[25]
Caddick, S.; Judd, D.B.; Lewis, A.K.D.; Reich, M.T.; Williams, M.R.V. Tetrahedron, 2003, 59(29), 5417-5423.
[26]
Remy, J.S.; Sirlin, C.; Vierling, P.; Behr, J.P. Bioconjugate. Chem., 1994, 5(6), 647-654.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 8
Year: 2019
Page: [615 - 618]
Pages: 4
DOI: 10.2174/1570178615666181022143627
Price: $65

Article Metrics

PDF: 38
HTML: 2