3016
F. Raffi et al.
PAPER
13C NMR (CDCl3): d = 202.7, 156.5, 136.6, 128.3, 127.8, 127.6,
MS (ESI): m/z = 756.8 [M + H]+.
66.30, 43.6, 41.3, 29.7, 28.8, 28.6, 28.5, 26.3.
Anal. Calcd for C38H73N7O8: C, 60.37; H, 9.73; N, 12.97. Found: C,
60.19; H, 9.92; N, 12.77.
MS (ESI): m/z = 300.0 [M + Na]+.
Anal. Calcd for C16H23NO3: C, 69.29; H, 8.36; N, 5.05. Found: C,
69.06; H, 8.61; N, 4.81.
1,17-Diguanidino-9-azaheptadecane Tris(trifluoroacetate)
[Iminoctadine Tris(trifluoroacetate, 1·3TFA]
A 10% soln of freshly distilled TFA in anhyd CH2Cl2 (3 mL) was
added to 3 (77 mg, 0.102 mmol) under argon at r.t. The mixture was
stirred at r.t. for 24 h and concentrated under reduced pressure giv-
ing 1 (71.1 mg, 100%) as a brown oil.
IR (CHCl3): 3467, 3355, 2927, 1662, 1408, 1203, 921 cm–1.
1H NMR (CD3OD): d = 3.17 (t, J = 7 Hz, 4 H), 2.96 (t, J = 8 Hz, 4
H), 1.66–1.61 (m, 4 H), 1.59–1.55 (m, 4 H), 1.36 (br s, 16 H).
13C NMR (CDCl3): d = 157.5, 48.7, 41.2, 29.5, 28.8, 28.6, 26.3,
26.2, 26.0.
MS (ESI): m/z = 356.1 [M + H]+.
1-[(Benzyloxycarbonyl)amino]-17-[2,3-bis(tert-butoxycarbon-
yl)guanidino]-9-azaheptadecane (4)
A soln of 5 (810.6 mg, 2.1 mmol) in anhyd DCE (10 mL) was added
dropwise to a stirred soln of aldehyde 6 (582 mg, 2.1 mmol) in an-
hyd DCE (20 mL) at r.t.. The mixture was stirred at r.t. and, after 10
min, NaB(OAc)3H (623 mg, 2.94 mmol) was added and it was
stirred at this temperature overnight. The mixture was concentrated
under reduced pressure, diluted with aq sat. NaHCO3 soln, and ex-
tracted with EtOAc (3 × 10 mL). The combined organic phases
were washed with brine and dried (Na2SO4). The solvent was evap-
orated under reduced pressure, and the residue was purified by flash
chromatography (MeOH–Et3N–EtOAc, 3:2:95), affording amine 4
(886.4 mg, 65%) as a yellow oil.
Anal. Calcd for C24H44F9N7O6: C, 41.32; H, 6.36; N, 14.05. Found:
C, 41.55; H, 6.6; N, 14.28.
IR (CHCl3): 3452, 3329, 2932, 1718, 1635, 1515, 1416, 1134, 1027,
914, 808 cm–1.
Acknowledgment
1H NMR (CDCl3): d = 8.23 (br s, NH), 7.29 (br s, 5 H), 5.04 (s, 2
H), 4.95 (br s, NH), 3.39–3.29 (m, 2 H), 3.17–3.07 (m, 2 H), 2.83–
2.75 (m, 4 H), 1.81–1.77 (m, 4 H), 1.45 (br s, 18 H), 1.27 (br s, 20
H).
13C NMR (CDCl3): d = 163.3, 156.2, 155.8, 153.0, 136.5, 128.2,
128.1, 127.7, 127.5, 127.4, 82.7, 78.9, 66.5, 47.3, 47.1, 40.7, 35.5,
29.6, 29.5, 28.9, 28.8, 28.7, 28.6, 28.0, 27.8, 26.5, 26.4, 25.5, 25.0.
We are grateful to Italian Ministero dell’Istruzione, dell’Università
e della Ricerca (PRIN Anno 2006-prot.2006030948_002). Techni-
cal assistance from Dr. Antonio Vivi director of NMR centre of
Siena University, Dr. Alessandra Zizzari for HPLC analysis. Dr.
Suvi Rajamäki (Ph.D.) is thanked for comments and suggestions for
the manuscript.
MS (ESI): m/z = 648.6 [M + H]+, 670.6 [M + Na]+.
References
Anal. Calcd for C35H61N5O6: C, 64.88; H, 9.49; N, 10.81. Found: C,
65.14; H, 9.68; N, 11.01.
(1) Fridkin, S. K.; Jarvis, W. R. Clin. Microbiol. Rev. 1996, 9,
499.
17-[2,3-Bis(tert-butoxycarbonyl)guanidino]-9-azaheptadecan-
1-amine (11)
A soln of 4 (335 mg, 0.517 mmol) in MeOH (10 mL) and 10% Pd-
C (335 mg) was reacted in a Parr apparatus under H2 (2.75 bar, 40
psi) at r.t. for 5 h. The mixture was filtered through Celite and the
solvent was evaporated under reduced pressure affording 11 (265.2
mg, 100%) as a pale yellow oil.
IR (CHCl3): 3331, 2933, 1715, 1634, 1416, 1369, 1134, 910 cm–1.
1H NMR (CDCl3): d = 8.20 (br s, NH), 3.36–3.30 (m, 2 H), 2.72–
2.66 (m, 6 H), 1.41 (br s, 9 H), 1.38 (br s, 9 H), 1.22–1.17 (m, 24 H).
(2) Toninello, A.; Pietrangeli, P.; De Marchi, U.; Salvi, M.;
Mondovì, B. Biochim. Biophys. Acta 2006, 1765, 1.
(3) Dreassi, D.; Zizzari, A. T.; D’Arezzo, S.; Visca, P.; Botta,
M. J. Pharmaceut. Biomed. Anal. 2007, 43, 1499.
(4) (a) Binda, C.; Angelini, R.; Federico, R.; Ascenzi, P.;
Mattevi, A. Biochemistry 2001, 40, 2766. (b) Cona, A.;
Manetti, F.; Leone, R.; Corelli, F.; Tavladoraki, P.;
Ponticelli, F.; Botta, M. Biochemistry 2004, 43, 3426.
(c) Binda, C.; Coda, A.; Angelini, R.; Federico, R.; Ascenzi,
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(5) Badcock, G. G.; Dyke, W. J. C. GB 1114155, 1968.
(6) Lavorenti, A.; Hudson, H. R.; Pianka, M. Quim. Nova 1998,
21, 130.
(7) Carmignani, M.; Volpe, A. R.; Botta, B.; Espinal, R.; De
Bonnevaux, S. C.; De Luca, C.; Botta, M.; Corelli, F.; Tafi,
A.; Sacco, R.; Delle Monache, G. J. Med. Chem. 2001, 44,
2950.
13C NMR (CDCl3): d = 163.8, 156.3, 153.5, 83.2, 79.4, 50.1, 41.2,
34.1, 29.9, 29.6, 29.4, 29.2, 28.6, 28.4, 28.2, 27.5, 27.0.
MS (ESI): m/z = 514.3 [M + H]+.
Anal. Calcd for C27H55N5O4: C, 63.12; H, 10.79; N, 13.63. Found:
C, 63.34; H, 10.99; N, 13.4.
(8) (a) Asada, T.; Miura, Y.; Yoshino, T. EP 0013554, 1980.
(b) Hudson, H. R.; Pianka, M.; Powroznik, L.; Lynch, V. P.
J. Labelled Compd. Radiopharm. 1980, 17, 1980.
(9) Hover, J. A.; Bock, C. W.; Bhat, K. L. Heterocycles 2003,
60, 791.
(10) Zehavi, U.; Sharon, N. J. Org. Chem. 1964, 29, 3654.
(11) Dess, D. D.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277.
(12) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849.
(13) Dardonville, C.; Rozas, I.; Goya, P.; Giron, R.; Goicoechea,
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Chem. 1998, 63, 3.
1,17-Bis[2,3-bis(tert-butoxycarbonyl)guanidino]-9-azahepta-
decane (3)
Et3N (67 mL, 0.48 mmol) and 1,3-bis(tert-butoxycarbonyl)-2-tri-
flylguanidine (188 mg, 0.48 mmol) were added to a stirred soln of
11 (226 mg, 0.44 mmol) in CH2Cl2 (8 mL), and the mixture was
stirred at r.t. for 6 h. The mixture was concentrated under reduced
pressure and purified by flash chromatography (MeOH–Et3N–
EtOAc, 3:2:95) affording 3 (265.7 mg, 80%) as a yellow oil.
IR (CHCl3): 3330, 2932, 1720, 1635, 1578, 1416, 1369, 1134, 1026,
908 cm–1.
1H NMR (CDCl3): d = 8.24 (br s, NH), 3.39–3.29 (m, 4 H), 2.55 (t,
J = 7 Hz, 4 H), 1.44 (br s, 36 H), 1.25 (br s, 24 H).
13C NMR (CDCl3): d = 163.8, 156.3, 153.5, 83.1, 79.4, 50.0, 41.1,
29.9, 29.5, 29.4, 29.1, 28.5, 28.3, 27.4, 26.9.
Synthesis 2007, No. 19, 3013–3016 © Thieme Stuttgart · New York