588 J. Am. Chem. Soc., Vol. 118, No. 3, 1996
CraVatt et al.
(m, 1H, CHHOH), 2.06 (q, 2H, J ) 6.8 Hz, CH2CHdCH), 1.28 (m,
20H), 0.89 (t, 3H, J ) 6.7 Hz, CH3); IR (neat) νmax 3435, 2923, 2848,
1682, 1677, 1205, 1184, 1137, 984, 802 cm-1; UV (CH3OH) λmax 228-
230 nm; FABHRMS (NBA-NaI) m/z 304.2624 (C18H35NO + Na+
requires 304.2616).
as a colorless oil (0.0095 g, 0.0101 g theoretical, 94%): 1H NMR (CD3-
OD, 400 MHz) δ 5.66 (m, 1H, CHdCH), 5.41-5.24 (m, 3H, CHdCH),
3.89 (m, 1H, H2NCH), 3.57-3.34 (m, 2H, HOCH2), 2.18-1.94 (m,
6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, 3H, J ) 6.7 Hz, CH3);
FABHRMS (NBA) m/z 282.2810 (C18H35NO + H+ requires 282.2797).
2(R)-Amino-1-hydroxy-3(Z),5(E)-octadecadiene (6): 1H NMR
(CD3OD, 400 MHz) δ 6.36 (m, 1H, CHdCH), 6.18 (t, 1H, J ) 11.3
Hz, CHdCH), 5.83 (p, 1H, J ) 7.5 Hz, CHdCH), 5.15 (t, 1H, J )
10.0 Hz, CHdCH), 4.04 (m, 1H, H2NCH), 3.55 (dd, 1H, J ) 3.6, 9.5
Hz, CHHOH), 3.30 (m, 1H, CHHOH), 2.13 (q, 2H, J ) 6.7 Hz, CH2-
CHdCH), 1.30 (m, 20H), 0.89 (t, 3H, J ) 6.7 Hz, CH3); IR (neat)
2(R)-Amino-1-hydroxy-3(E),12(Z)-octadecadiene (20). A solution
of (2R,3Z,12Z)-61 (0.010 g, 0.036 mmol) in TFA-H2O (3:1 ratio, 0.200
mL, 0.18 M) was stirred at 25 °C for 10 min. The reaction mixture
was treated dropwise with saturated aqueous NaHCO3 and partitioned
between EtOAc (50 mL) and H2O (50 mL). The organic layer was
dried (Na2SO4) and concentrated under reduced pressure to provide 20
as a colorless oil (0.0064 g, 0.0067 g theoretical, 96%): 1H NMR (CD3-
OD, 250 MHz) δ 5.69 (m, 1H, CHdCH), 5.43-5.30 (m, 3H, CHdCH),
3.53 (m, 1H, H2NCH), 3.36 (m, 2H, HOCH2), 2.07-1.94 (m, 6H, CH2-
CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, 3H, J ) 6.7 Hz, CH3);
FABHRMS (NBA-NaI) m/z 304.2609 (C18H35NO + Na+ requires
304.2616).
νmax 3343, 2923, 2851, 1682, 1205, 1184, 1138, 984, 948, 805 cm-1
;
UV (CH3OH) λmax 228-230 nm; FABHRMS (NBA-CsI) m/z 414.1758
(C18H35NO + Cs+ requires 414.1773).
2(R)-Amino-1-hydroxy-3(E),5(Z)-octadecadiene (7): 1H NMR
(CD3OD, 400 MHz) δ 6.64 (dd, 1H, J ) 4.4, 11.1 Hz, CHdCH), 5.98
(t, 1H, J ) 10.9 Hz, CHdCH), 5.59 (m, 1H, CHdCH), 5.47 (q, 1H,
J ) 8.8 Hz, CHdCH), 3.65-3.40 (m, 3H, H2NCH and CH2OH), 2.20
(q, 2H, J ) 7.2 Hz, CH2CHdCH), 1.30 (m, 20H), 0.89 (t, 3H, J ) 6.7
Hz, CH3); IR (neat) νmax 3353, 2923, 2851, 1676, 1205, 1179, 1133,
984, 948, 800 cm-1; UV (CH3OH) λmax 232-234 nm; FABHRMS
(NBA-CsI) m/z 414.1760 (C18H35NO + Cs+ requires 414.1773).
2(R)-Amino-1-hydroxy-3(Z),5(Z)-octadecadiene (8): 1H NMR
(CD3OD, 400 MHz) δ 6.47 (t, 1H, J ) 11.4 Hz, CHdCH), 6.29 (t,
1H, J ) 11.4 Hz, CHdCH), 5.61 (m, 1H, CHdCH), 5.29 (t, 1H, J )
10.2 Hz, CHdCH), 3.98 (m, 1H, H2NCH), 3.55 (dd, 1H, J ) 4.3, 10.8
Hz, CHHOH), 3.39 (m, 1H, CHHOH), 2.20 (q, 2H, J ) 7.2 Hz, CH2-
CHdCH), 1.30 (m, 20H), 0.89 (t, 3H, J ) 6.7 Hz, CH3); IR (neat)
The deprotections to provide 9-24 were conducted following the
procedures for 19-20.
2(R)-Amino-1-hydroxy-3(Z),6(E)-octadecadiene (9): 1H NMR
(CD3OD, 250 MHz) δ 5.76-5.25 (m, 4H, CHdCH), 3.91 (m, 1H, H2-
NCH), 3.59-3.32 (m, 2H, HOCH2), 2.84 (m, 2H, CHCH2CH), 2.04
(m, 2H, CHCH2CH2), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz, 3H,
CH3); electrospray MS m/z 282, 304 (C18H35NO + H+ requires 282,
C18H35NO + Na+ requires 304).
2(R)-Amino-1-hydroxy-3(Z),7(Z)-octadecadiene (10): 1H NMR
(CD3OD, 400 MHz) δ 5.66 (m, 1H, CHdCH), 5.41-5.24 (m, 3H,
CHdCH), 3.89 (m, 1H, H2NCH), 3.57-3.34 (m, 2H, HOCH2), 2.18-
1.94 (m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz,
3H, CH3); IR (neat) νmax 3364, 2923, 2851, 1677, 1205, 1138, 1056,
800 cm-1; FABHRMS (NBA) m/z 282.2784 (C18H35NO + H+ requires
282.2797).
2(R)-Amino-1-hydroxy-3(Z),8(Z)-octadecadiene (11): 1H NMR
(CD3OD, 400 MHz) δ 5.66 (m, 1H, CHdCH), 5.41-5.24 (m, 3H,
CHdCH), 3.89 (m, 1H, H2NCH), 3.57-3.34 (m, 2H, HOCH2), 2.18-
1.94 (m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz,
3H, CH3); IR (neat) νmax 3364, 2923, 2851, 1677, 1205, 1138, 1056,
800 cm-1; FABHRMS (NBA-CsI) m/z 414.1786 (C18H35NO + Cs+
requires 414.1773).
2(R)-Amino-1-hydroxy-3(E),8(Z)-octadecadiene (12): 1H NMR
(CD3OD, 400 MHz) δ 5.69 (m, 1H, CHdCH), 5.43-5.30 (m, 3H,
CHdCH), 3.53 (m, 1H, H2NCH), 3.36 (m, 2H, HOCH2), 2.07-1.94
(m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz, 3H,
CH3); IR (neat) νmax 3364, 2923, 2851, 1677, 1205, 1138, 1056, 969,
800 cm-1; electrospray MS m/z 282, 304 (C18H35NO + H+ requires
282, C18H35NO + Na+ requires 304).
2(R)-Amino-1-hydroxy-3(Z),9(Z)-octadecadiene (13): 1H NMR
(CD3OD, 400 MHz) δ 5.66 (m, 1H, CHdCH), 5.41-5.24 (m, 3H,
CHdCH), 3.89 (m, 1H, H2NCH), 3.57-3.34 (m, 2H, HOCH2), 2.18-
1.94 (m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz,
3H, CH3); IR (neat) νmax 3364, 2923, 2851, 1677, 1205, 1138, 1056,
800 cm-1; FABHRMS (NBA-CsI) m/z 414.1760 (C18H35NO + Cs+
requires 414.1773).
ν
max 3353, 2923, 2851, 1682, 1205, 1179, 1138, 800 cm-1; UV (CH3-
OH) λmax 232-234 nm; FABHRMS (NBA-CsI) m/z 414.1761 (C18H35-
NO + Cs+ requires 414.1773).
3-(tert-Butyloxycarbonyl)-2,2-dimethyl-4(R)-[1(Z),10(Z)-hexadec-
adienyl]oxazolidine [(2R,3Z,12Z)-61] and 3-(tert-Butyloxycarbonyl)-
2,2-dimethyl-4(R)-[1(E),10(Z)-hexadecadienyl]oxazolidine [(2R,3E,
12Z)-61]. A solution of 4629 (0.235 g, 0.39 mmol, 1.0 equiv) in THF
(2.0 mL, 0.2 M) at -78 °C was treated with n-BuLi (0.173 mL, 2.5 M
solution in hexanes, 0.43 mmol, 1.1 equiv). The bright orange-red
reaction mixture was warmed to 25 °C and stirred for 10 min. The
reaction mixture was recooled to -78 °C, (S)-31 (0.107 g, 0.47 mmol,
1.2 equiv) was added, and the reaction mixture was warmed to 25 °C.
After being stirred at 25 °C for 30 min, the reaction mixture was treated
with saturated aqueous NH4Cl and partitioned between EtOAc (50 mL)
and H2O (50 mL). The organic layer was dried (Na2SO4) and
concentrated under reduced pressure. Chromatography (SiO2, 3 × 15
cm, 0-2% EtOAc-hexane gradient elution) afforded (3Z,12Z)-61
(0.095 g) and a 1:1 mixture of (3Z,12Z)- and (3E,12Z)-61 (0.0021 g,
0.116 g total yield, 0.165 g theoretical, 70%) as colorless oils. A second
chromatography (SiO2, 3 × 15 cm, 0-1% EtOAc-hexane gradient
elution) on the remaining mixture provided the olefin isomers cleanly
separated from one another.
(2R,3Z,12Z)-61: 1H NMR (CDCl3, 250 MHz) δ 5.57-5.25 (m, 4H,
CHdCH), 4.62 (m, 1H, RNCH), 4.05 (dd, J ) 6.2, 8.6 Hz, 1H, OCHH),
3.64 (dd, J ) 3.3, 8.7 Hz, 1H, OCHH), 2.23-1.88 (m, 6H, CH2-
CHdCH), 1.70-1.18 (m, 31H), 0.89 (t, J ) 6.7 Hz, 3H, CH3); [R]25
D
2(R)-Amino-1-hydroxy-3(E),9(Z)-octadecadiene (14): 1H NMR
(CD3OD, 400 MHz) δ 5.69 (m, 1H, CHdCH), 5.43-5.30 (m, 3H,
CHdCH), 3.53 (m, 1H, H2NCH), 3.36 (m, 2H, HOCH2), 2.07-1.94
(m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz, 3H,
CH3); IR (neat) νmax 3364, 2923, 2851, 1677, 1205, 1138, 1056, 969,
800 cm-1; FABHRMS (NBA-CsI) m/z 414.1756 (C18H35NO + Cs+
requires 414.1773).
+60 (c 1.15, THF); IR (neat) νmax 2925, 2854, 1701, 1383, 1250, 1175,
1089, 850 cm-1; FABHRMS (NBA-CsI) m/z 554.2635 (C26H47NO3
+ Cs+ requires 554.2610).
(2R,3E,12Z)-61: 1H NMR (CDCl3, 250 MHz) δ 5.71-5.25 (m, 4H,
CHdCH), 4.22 (m, 1H, RNCH), 3.99 (dd, J ) 6.0, 8.7 Hz, 1H, OCHH),
3.70 (dd, J ) 2.1, 8.7 Hz, 1H, OCHH), 2.16-1.90 (m, 6H, CH2-
CHdCH), 1.70-1.18 (m, 31H), 0.89 (t, J ) 6.7 Hz, 3H, CH3); IR
1
(neat) νmax 2925, 2864, 1701, 1383, 1250, 1175, 1089, 965, 850 cm-1
;
2(R)-Amino-1-hydroxy-3(Z),10(Z)-octadecadiene (15): H NMR
FABHRMS (NBA-NaI) m/z 444.3465 (C26H47NO3 + Na+ requires
444.3454).
(CD3OD, 400 MHz) δ 5.66 (m, 1H, CHdCH), 5.41-5.24 (m, 3H,
CHdCH), 3.89 (m, 1H, H2NCH), 3.57-3.34 (m, 2H, HOCH2), 2.18-
1.94 (m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz,
3H, CH3); IR (neat) νmax 3364, 2923, 2851, 1677, 1205, 1138, 1056,
800 cm-1; FABHRMS (NBA) m/z 282.2806 (C18H35NO + H+ requires
282.2797).
Intermediates 56-6329 were obtained by the procedure detailed for
61.
2(R)-Amino-1-hydroxy-3(Z),12(Z)-octadecadiene (19). A solution
of (2R,3Z,12Z)-61 (0.015 g, 0.036 mmol) in TFA-H2O (3:1, 0.200
mL, 0.18 M) was stirred at 25 °C for 10 min. The reaction mixture
was treated dropwise with saturated aqueous NaHCO3 and partitioned
between EtOAc (50 mL) and H2O (50 mL). The organic layer was
dried (Na2SO4) and concentrated under reduced pressure to provide 19
1
2(R)-Amino-1-hydroxy-3(E),10(Z)-octadecadiene (16): H NMR
(CD3OD, 400 MHz) δ 5.69 (m, 1H, CHdCH), 5.43-5.30 (m, 3H,
CHdCH), 3.53 (m, 1H, H2NCH), 3.36 (m, 2H, HOCH2), 2.07-1.94
(m, 6H, CH2CHdCH), 1.49-1.22 (m, 16H), 0.89 (t, J ) 6.7 Hz, 3H,