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solid. MP 108–110 uC [lit.11a M.p. 107–109 uC; [a]2D5: 23.5 (c 0.9,
MeOH) [lit.11[a]D 25: 24.5 (c 1.5, MeOH); IR (CHCl3, cm21): nmax
0.87–0.83 (m, 3H); 13C NMR (100 MHz, CDCl3): 70.6, 51.6, 32.9,
32.0, 29.7, 29.6, 29.4, 29.0, 25.9, 22.6, 17.0, 13.4; MS (ESI): m/z
308 [M + Na]+.
1
3389, 2928, 1610, 1500, 1025, 721; H NMR (400 MHz, MeOH-
D4): d 3.64–3.58 (m, 2H), 3.17–3.14 (m, 1H), 1.22–1.17 (m,
16H), 1.10 (d, J = 6.83 Hz, 3H), 0.85–0.80 (m, 3H); 13C NMR
(100 MHz, CDCl3):70. 7, 51.6, 32.9, 32.0, 29.7, 29.6, 25.5, 29.4,
29.0, 25.9, 22.7, 13.4, 12.2; MS (ESI): m/z 224 [M + Na]+.
Acknowledgements
M. P. and P. S. C. thank DST and CSIR, New Delhi respectively
for the award of research fellowship. We also thank Mrs. S.
Kunte for HPLC analysis.
Clavaminol C (1b)
To a solution of 1a (30 mg, 0.14 mmol) in Et3N (0.06 mL) was
added pentafluorophenyl acetate (0.10 g, 0.44 mmol), and the
reaction mixture was stirred at room temperature for 1.5 h.
The solvent was removed by evaporation under vacuum, and
the residue was purified by flash chromatography on silica
(EtOAc/MeOH = 95/5) to give 1b (28 mg, 80%) as a white solid.
Mp 104–106 uC [lit.11Mp. 103–105 uC; [a]2D5: +10.51 (c 1.5,
Notes and references
1 (a) For leading references on ceramides, see: K. Hanada,
K. Kumagai, N. Tomishige and M. Kawano, Biochim.
Biophys. Acta., 2007, 1771, 644; (b) J. A. Bouwstra and
M. Ponec, Biochim. Biophys. Acta, Biomembr., 2006, 1758,
2080.
2 T. Natori, M. Morita, K. Akimoto and Y. Koezuka,
Tetrahedron, 1994, 50, 2771.
3 S. Ladisch, R. Li and E. Olson, Proc. Natl. Acad. Sci. U. S. A.,
1994, 91, 1974.
4 (a) A. Copani, D. Melchiorri, A. Caricasole, F. Martini,
P. Sale, R. Carnevale, R. Gradini, M. A. Sortino, L. Lenti,
R. De Maria and F. Nicoletti, J. Neurosci., 2002, 22, 3963; (b)
T. Kolter and K. Sandhoff, Angew. Chem., Int. Ed., 1999, 38,
1532.
5 (a) H. Higashi and N. H. Chen, Glycoconjugate J., 2004, 20,
49; (b) F. Vaccarino, A. Guidotti and E. Costa, Proc. Natl.
Acad. Sci. U. S. A., 1987, 84, 8707.
6 S. De Jonghe, I. Van Overmeire, S. van Calenbergh,
C. Hendrix, R. Busson, D. de Keukeleire and
P. Herdewijn, Eur. J. Org. Chem., 2000, 3177.
7 (a) A. Aiello, E. Fattorusso, A. Giordano, M. Menna,
C. Navarrete and E. Munoz, Bioorg. Med. Chem., 2007, 15,
2920; (b) A. Aiello, E. Fattorusso, A. Giordano, M. Menna,
C. Navarrete and E. Munoz, Tetrahedron, 2009, 65, 4384.
8 Clavaminol A has an IC50 value of approximately 5 mg
mL21 against AGS cells. It has a similar level of cytotoxicity
against T47D and A549 cells.
CHCl3) [lit.11a [a]D25 = +11.1 (c 2.1, MeOH)]; IR(CHCl3, cm21
)
3283, 2918, 1645, 1558, 1467, 1126, 747; 1H NMR (400 MHz,
CDCl3): d 5.79–5.71 (m, 1H), 4.07–4.04 (m, 1H), 3.65–3.58 (m,
1H), 2.31–2.24 (s, 1H), 1.99 (s, 3H), 1.22–1.20 (m, 16H), 1.07 (d,
J = 6.8 Hz, 3H), 0.82 (t, J = 7.02 Hz, 3H); 13C NMR (100 MHz,
CDCl3): 169.9, 73.8, 49.4, 33.7, 31.9, 29.7, 29.6, 29.5, 29.3, 25.9,
23.5, 22.7, 14.1, 13.9; MS (ESI): m/z 266 [M + Na]+.
Clavaminol H (1c)
To a solution of 20 (30 mg, 0.12 mmol) in Et3N (0.05 mL) was
added pentafluorophenyl acetate (87 mg, 0.38 mmol), and the
reaction mixture was stirred at rt for 1.5 h. The solvent was
removed by evaporation under vacuum, and the residue was
purified by flash chromatography on silica (EtOAc/MeOH = 95/
5) to give 1c (24 mg, 75%) as a white solid. Mp 106–108 uC
[lit.11h M.p. 107–109 uC; [a]D25 = +3.6 (c 1.5, MeOH) [lit.11 [a]D23
=
+3.3 (c 1.4, MeOH)]; IR(CHCl3, cm21) 3283, 2918, 1645, 1558,
1
1373, 1095; H NMR (400 MHz, CDCl3): d 5.85–5.81 (m, 1H),
4.11–4.10 (m, 1H), 3.68–3.61 (m, 3H), 2.38–2.27 (m, 2H), 2.03
(s, 3H), 1.24 (br s, 16H), 0.86 (t, J = 6.27 Hz, 3H); 13C NMR (100
MHz, CDCl3): 169.9, 74.2, 60.4, 49.4, 33.7, 31.9, 29.7, 29.3, 25.9,
23.5, 22.7, 14.1; MS (ESI): m/z 282 [M + Na]+.
Sphinganine (2)
9 J. L. Acena, J. Adrio, C. Cuevas, P. Gallego, I. Manzanares,
S. Munt and I. Rodriguez, Antitumoral compounds, U.S.
Patent 048834A1, 2004.
The procedure is same as mentioned above for (2R, 3S)-2-
aminododecane-1, 3-diol (20) to give sphinganine (2) (17 mg,
99%) as a white solid: mp 90–91 uC (lit.11h mp 89–90 uC); [a]D25:
+9.8 (c 0.04, MeOH) [lit.11[a]2D5: +10.0 (c 0.06, MeOH)]. IR
(CHCl3, cm21): nmax 3282, 2915, 2848, 1726, 1679, 1526, 1429,
1259, 1055, 836; 1H NMR (500 MHz, MeOH-D4): d 4.43–4.36 (m,
1H), 4.28–4.04 (m, 1H), 3.96–3.71 (m, 1H), 3.52–3.46 (m, 1H),
2.06–2.02 (m, 2H), 1.59–1.00 (m, 26H), 0.91 (br s, 3H); 13C NMR
(125 MHz, CDCl3):72.18, 66.91, 60.37, 57.11, 32.92, 31.89,
29.61, 29.29, 25.45, 22.56, 13.28; MS (ESI): m/z 324 [M + Na]+.
10 A. M. Sanchez, S. Malagarie-Cazenave, N. Olea, D. Vara,
´
C. Cuevas and I. Dıaz-Laviada, Eur. J. Pharmacol., Mol.
Pharmacol. Sect., 2008, 584, 237.
11 (a) For recent references on the synthesis of clavaminols,
see: M. Zaed Ahmed and A. Sutherland, Org. Biomol. Chem.,
2011, 9, 8030; (b) B. S. Chen, L. Yang, J. L. Ye, T. Huang, Y.
P. Ruan, J. Fu and P. Q. Huang, Eur. J. Med. Chem., 2011,
46, 5480; (c) For recent references on the synthesis of
sphingamine derivatives, see: C. Seguin, F. Ferreira,
B. Botuha, F. Chemla and A. J. Perez-Luna, J. Org. Chem.,
2009, 74, 6986; (d) Y. W. Zhong, Y. Z. Dong, K. Fang,
K. Izumi, M.-H. Liu and G. -Q. Lin, J. Am. Chem. Soc., 2005,
127, 11956; (e) R. M. Ndonye, D. P. Izmirian, M. F. Dunn, K.
O. A. Yu, S. A. Porcelli, A. Khurana, M. Kronenberg, S.
K. Richardson and A. R. Howell, J. Org. Chem., 2005, 70,
10260; (f) D. Enders and A. MJuller-HJuwen, Eur. J. Org.
Chem., 2004, 1732; (g) E. Abraham, S. G. Davies, N.
(+)-Spisulosine (3)
The procedure is same as mentioned above for clavaminol A
(1a) to give (+)-spisulosine (3) (20 mg, 99%) as a white solid.
Mp. 65–67 uC [lit.11i Mp. 64.5–66 uC; [a]D25: +19.3 (c 0.32, CHCl3)
11
[lit. [a]2D5 + 21.4 (c 0.5, CHCl3). IR (CHCl3, cm21): nmax 3408,
3345, 3200, 2922, 2854, 1652, 1468, 1257, 1190, 1070, 1044,
1
744, 621; H NMR (400 MHz, MeOH-D4): d 3.71–3.65 (m, 1H),
3.24–3.21 (m, 1H), 1.42–1.24 (m, 31H), 1.17 (d, J = 6.78 Hz, 3H),
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