C. Bello et al. / Bioorg. Med. Chem. 19 (2011) 7720–7727
7725
2J = 12.0, 1H, HH–C(5)) 1.59 (m, 2H, H2-C(2) hep) 1.32–1.39 (m, 8H,
4.3.6. 1,4-Dideoxy-5-O-[(9Z)-hexadec-9-en-1-yl]-1,4-imino-
ribitol 18
General procedure 1. TBI: 0.132 g, 0.36 mmol, 1.3 equiv, R-X: pal-
mitoleyl methanesulfonate (0.5 ml excess), 12: 0.074 g, 0.27 mmol,
NaOH: 0.11 ml. Pure N-tert-butoxycarbonyl-1,4-dideoxy-2,3-O-
D-
C(2)-(CH2)4-C(7) hep) 0.91 (t, 3J = 6.8, 3H, H3-C(7) hep). 13C NMR
(101 MHz, MeOH-d4): d 74.7 (d, 1J = 147, C(3)) 72.6 (t, 1J = 139,
C(6)) 72.5 (d, 1J = 149, C(4)) 71.8 (t, 1J = 142, C(1) hep) 63.3 (d,
1J = 140, C(2)) 52.4 (t, 1J = 140, C(5)) 33.0 (t, 1J = 124, C(2) hep)
30.7 (t, 1J = 123, C(3) hep) 30.3 (t, 1J = 124, C(4) hep) 29.2 (t,
1J = 126, C(5) hep) 23.7 (t, 1J = 124, C(6)hep) 14.4 (q, 1J = 124, C(7)
hep). HR-ESI-MS: calcd for C12H25NO3: 232.1907, found 232.1914
([M+H]+).
isopropylidene-5-O-[(9Z)-hexadec-9-en-1-yl]-1,4-imino-D-ribitol
was obtained (0.090 g, 0.18 mmol, 67% yield) as a colourless oil
(flash column chromatography: PE/AcOEt 7:1). Deprotection per-
formed following the general procedure 2: protected 18: 0.090 g,
0.18 mmol TFA: 0.34 ml. Pure 18 (0.054 g, 0.15 mmol, 84% yield)
was obtained as a white foam after flash column chromatography
4.3.4. 1,4-Dideoxy-5-O-decyl-1,4-imino-D-ribitol 16
25
on silica gel (CH2Cl2/MeOH 9:1, 1% NH3 aq). ½a D25
ꢃ
+21; ½
a
ꢃ
+50;
577
General procedure 1. TBI: 0.163 g, 0.44 mmol, 1.2 equiv, R–X: de-
cyl bromide (0.5 ml, excess), 12: 0.098 g, 0.36 mmol; NaOH: 0.2 ml.
Pure N-tert-butoxycarbonyl-1,4-dideoxy-2,3-O-isopropylidene-5-
O-decyl-1,4-imino-D-ribitol was obtained (0.050 g, 0.12 mmol,
34% yield) as a colourless oil (flash column chromatography: petro-
leum ether/ ethyl acetate 9:1).
25
435
25
405
½
aꢃ
+46; ½
a
ꢃ
+48 (c = 0.1160, CHCl3). IR (pure): 3313, 3257,
2913, 2848, 1080, 1034, 874. 1H NMR (400 MHz, CDCl3, pal = pal-
mitoleyl): d 5.44 (m, 2H, H–C(9) and H–C(10) pal) 4.14 (m, 1H, H–
C(4)) 3.89 (m, 1H, H–C(3)) 3.69 (br s 3H, 2 xH–O and H-N) 3.57
(dd, 2J = 9.7, 3J = 4.5, 1H, HHC(6)) 3.53 (dd, 2J = 9.7, 3J = 5.2, 1H,
HHC(6)) 3.44 (t, 3J = 6.7, 2H, H2C(1) pal) 3.24 (dd, 2J = 12.0,
3J = 5.1, 1H, HHC(5)) 3.17 (m, 1H, H–C(2)) 2.96 (dd, 2J = 9.7,
3J = 3.0, 1H, HHC(5)) 2.00 (m, 4H, H2C(8) and H2C(11) pal) 1.55
(m, 2H, H2C(2) pal) 1.28 (br s, 18H, C(2)-(CH2)5-C(8) and C(11)-
(CH2)4-C(16) pal) 0.88 (t, 3J = 6.8, 3H, H3C(16) pal). 13C NMR
(101 MHz, CDCl3, pal = palmitoleyl): d 129.9 (d, 1J = 153, C(9)
pal) 129.8 (d, 1J = 153, C(10) pal) 74.1 (d, 1J = 146, C(3)) 71.7 (t,
1J = 139, C(1) pal) 71.4 (d, 1J = 150, C(4)) 70.8 (t, 1J = 142, C(6))
62.1 (d, 1J = 138, C(2)) 51.8 (t, 1J = 138, C(5)) 31.7 (t, 1J = 127,
H2C pal) 29.7 (t, 1J = 125, H2C pal) 29.7 (t, 1J = 124, H2C pal) 29.5
(t, 1J = 124, H2C pal) 29.5 (t, 1J = 124, H2C pal) 29.4 (t, 1J = 124,
H2C pal) 29.3 (t, 1J = 124, H2C pal) 28.9 (t, 1J = 124, H2C pal) 27.2
(t, 1J = 124, H2C pal) 27.2 (t, 1J = 124, H2C pal) 26.1 (t, 1J = 125,
H2C pal) 22.6 (t, 1J = 124, H2C pal) 14.1 (q, 1J = 124, C(16) pal).
HR-ESI-TOF-MS: calcd for C21H41NO3: 356.3159, found 356.2715
([M+H]+).
Deprotection performed following the general procedure 2:
protected 16: 0.050 g, 0.12 mmol, TFA: 0.5 ml. Pure 16
(0.0252 g, 0.09 mmol, 77% yield) was obtained as a white foam
after flash column chromatography on silica gel (CH2Cl2/MeOH
9:1, 1% NH3 aq).
25
577
25
435
25
405
½
a 2D5
ꢃ
+31; ½
a
ꢃ
+23; ½
aꢃ
+57; ½
aꢃ
+77 (c = 0.0575, MeOH). IR
(pure): 3511, 3268, 2917, 2850, 1078, 982, 874. 1H NMR (400 MHz,
CDCl3, dec = decyl): d 4.12 (m, 1H, H–C(4)) 3.86 (m, 1H, H–C(3))
3.54 (m, 2H, H2-C-C(2)) 3.44 (t, 3J = 6.7, 2H, H2-C(1) dec) 3.28 (m,
2H, 2ꢂ H–O) 3.22 (dd, 2J = 12.0, 3J = 5.1, 1H, HH–C(5)) 3.11 (m,
1H, H–C(2)) 2.90 (dd, 2J = 12.0, 3J = 3.1, 1H, HH–C(5)) 1.55 (m, 2H,
H2-C(2) dec) 1.26 (br s 14H, C(2)-(CH2)7-C(10) dec) 0.88 (t,
3J = 6.7, 3H, H2-C(10) dec). 13C NMR (101 MHz, CDCl3): d 74.4 (d,
1J = 143, C(3)) 71.6 (t, 1J = 139, C(1) dec) 71.5 (d, 1J = 149, C(4))
71.2 (t, 1J = 139, H2C-C(2)) 62.2 (d, 1J = 139, C(2)) 52.0 (t, 1J = 139,
C(5)) 31.9 (t, 1J = 122, C(2) dec) 29.6 (t, 1J = 124, C(4) and C(3)
dec) 29.6 (t, 1J = 125, C(5) dec) 29.5 (t, 1J = 125, C(6) dec) 29.3 (t,
1J = 124, C(7) dec) 26.1 (t, 1J = 124, C(8) dec) 22.7 (t, 1J = 124, C(9)
dec) 14.1 (q, 1J = 124, C(10) dec). HR-ESI-TOF-MS: calcd for
4.3.7. 1,4-Dideoxy-5-O-[(9Z,12Z)-octadeca-9,12-dien-1-yl]-1,4-
imino-D-ribitol 19
General procedure 1. TBI: 0.153 g, 0.41 mmol, 1.2 equiv, R-X: lino-
leyl methanesulfonate (0.5 ml, excess), 12: 0.090 g, 0.33 mmol,
NaOH: 0.12 ml. Pure N-tert-butoxycarbonyl-1,4-dideoxy-2,3-O-iso-
C
15H31NO3: 274.2382, found 274.2381 ([M+H]+).
4.3.5. 1,4-Dideoxy-5-O-tetradecyl-1,4-imino- -ribitol 17
D
propylidene-5-O-[(9Z,12Z)-octadeca-9,12-dien-1-yl]-1,4-imino-D-
General procedure 1. TBI: 0.100 g, 0.27 mmol, 1 equiv, R-X: tetra-
decyl methanesulfonate (0.412 g, 1.41 mmol, 5.2 equiv), CH3CN
(0.5 ml) 12: 0.073 g, 0.27 mmol, NaOH: 0.25 ml. Pure N-tert-butox-
ycarbonyl-1,4-dideoxy-2,3-O-isopropylidene-5-O-tetradecyl-1,4-
ribitol was obtained (0.086 g, 0.17 mmol, 52% yield) as a colourless
oil (flash column chromatography: PE/AcOEt 7:1). Deprotection per-
formed following the general procedure 2: protected 19: 0.090 g,
0.18 mmol TFA: 0.34 ml. Pure 19 (0.039 g, 0.10 mmol, 61% yield)
imino-D-ribitol was obtained (0.046 g, 0.1 mmol, 37% yield) as a
was obtained as a white foam after flash column chromatography
25
on silica gel (CH2Cl2/MeOH 9:1, 1% NH3 aq). ½a D25
ꢃ
+35 ½ ꢃ
a
colourless oil (flash column chromatography: PE/ AcOEt 93:7).
Deprotection performed following the general procedure 2: pro-
tected 17: 0.046 g, 0.1 mmol, TFA: 0.4 ml. Pure 17 (0.021 g,
0.063 mmol, 63% yield) was obtained as a white foam after flash
column chromatography on silica gel (CH2Cl2/MeOH 9:1, 1% NH3
577
25
435
½
aꢃ
½
a 2D5
(c = 0.1460, MeOH) IR (pure): 3293, 3202, 2918, 2850,
ꢃ
1094, 1079, 981, 827, 720. 1H NMR (400 MHz, CDCl3, lin = linoleyl):
d 5.39–5.30 (m, 4H, H–C(9), H–C(10), H–C(12) and H–C(13) lin) 4.28
(m, 3H, 2ꢂ H–O and H-N) 4.18 (m, 1H, H–C(2)) 3.96 (m, 1H, H–C(3))
3.61 (dd, 2J = 9.7, 3J = 4.1, 1H, HHC(5)) 3.55 (dd, 2J = 9.7, 3J = 5.1, 1H,
HHC(5)) 3.45 (m, 2H, H2C(1) lin) 3.29–3.25 (m, 2H, H–C(4) and
HHC(1)) 3.08 (bd, dd, 2J = 10.2, 1H, HHC(1)) 2.77 (m, 2H, H2C(11)
lin) 2.05 (m, 4H, H2C(8) and H2C(14) lin) 1.54 ((m, 2H, H2C(2) lin)
1.30 (m, 16H, C(2)-(CH2)5-C(8) and C(14)-(CH2)3-C(18) lin) 0.89 (t,
3J = 6.8, 3H, H3C(18) lin). 13C NMR (101 MHz, CDCl3, lin = linoleyl):
d 130.2 (d, 1J = 161, C(9) lin) 130.1 (d, 1J = 161, C(10) lin) 128.0 (d,
1J = 149, C(12) lin) 127.9 (d, 1J = 149, C(13) lin) 74.0 (d, 1J = 143,
C(3)) 71.7 (t, 1J = 142, C(1) lin) 71.2 (d, 1J = 149, C(2)) 70.2 (t,
1J = 143, C(5)) 62.0 (d, 1J = 126, C(4)) 51.5 (t, 1J = 146, C(1)) 31.5 (t,
H2C lin) 29.7 (t, H2C lin) 29.5 (t, 1J = 125, H2C lin) 29.5 (t, 1J = 125,
H2C lin) 29.5 (t, 1J = 125, H2C lin) 29.3 (t, 1J = 120, H2C lin) 29.3 t,
1J = 120, H2C lin) 27.2 (t, H2C lin) 27.2 t, H2C lin) 26.1 (t, 1J = 124,
H2C lin) 25.6 (t, 1J = 125, H2C lin) 22.5 (t, 1J = 117, H2C lin) 14.0 (q,
1J = 123, C(18) lin). HR-ESI-TOF-MS: calcd for C23H43NO3:
382.3316, found 382.3544 ([M+H]+).
25
577
25
435
25
405
aq). ½a 2D5
ꢃ
+27; ½
aꢃ
+25; ½
aꢃ
+50; ½
aꢃ
+65 (c = 0.052, MeOH).
IR (neat): 3417, 3280, 3239, 2917, 2849, 1470, 1376, 1341, 1125,
1094, 832, 718. 1H NMR (400 MHz, CDCl3, td = tetradecyl): d
4.12 (m, 1H, H–C(4)) 3.86 (m, 1H, H–C(3)) 3.49–3.56 (m, 2H,
H2C-C(2)) 3.44 (t, 3J = 6.7, 2H, H–C(1) td) 3.22 (dd, 2J = 12.0,
3J = 5.1, 2H, HHC(5) and H–O) 3.10–3.14 (m, 2H, H–C(2) and H–
O) 2.91 (dd, 2J = 12.0, 3J = 5.1, 1H, HHC(5)) 1.55 (m, 2H, H2C(2)
td) 1.26 (m, 22H, (CH2)11 td) 0.88 (t, 3J = 6.5, 3H, H3C(14) td). 13C
NMR (100 MHz, CDCl3, td = tetradecyl): d 74.4 (d, 1J = 145, C(3))
71.7 (t, 1J = 141, C(1) td) 71.6 (d, 1J = 150, C(4)) 71.3 (t, 1J = 141,
H2C-C(2)) 62.2 (d, 1J = 137, C(2)) 52.0 (t, 1J = 138, C(5)) 31.9 (t,
1J = 124, CH2 td) 29.7 (t, 1J = 124, (CH2)2 td) 29.6 (t, 1J = 124,
(CH2)2 td) 29.6 (t, 1J = 124, CH2 td) 29.6 (t, 1J = 124, CH2 td) 29.6
(t, 1J = 124, CH2 td) 29.3 (t, 1J = 124, CH2 td) 26.1 (t, 1J = 125, CH2
td) 22.7 (t, 1J = 127, CH2 td) 14.1 (q, 1J = 124, C(14) td). HR-ESI-
MS: calcd for C19H39NO3: 330.3003, found: 330.2991 ([M+H]+).