sequentially with sat aq CuSO4 (2 × 10 mL), H2O (10 mL) and
brine (10 mL), dried and concentrated in vacuo. Recrystallisation
from CHCl3–pentane (1 : 1) gave 55 as a white solid (13 mg, 87%,
Synthesis, 1998, 1075. For a review of the synthesis of phytosphingosine
see: A. R. Howell and A. J. Ndakala, Curr. Org. Chem., 2002, 6, 365.
6 For the enantiospecific synthesis of sphinganine and/or sphingosine
see: H. Azuma, S. Tamagaki and K. Ogino, J. Org. Chem., 2000, 65,
3538; R. I. Duclos, Chem. Phys. Lipids, 2001, 111, 111; T. Nakamura
and M. Shiozaki, Tetrahedron, 2001, 57, 9087; J. Chun, G. Li, H.-S.
Byun and R. Bittman, Tetrahedron Lett., 2002, 43, 375; J. E. Milne, K.
Jarowicki, P. J. Kocienski and J. Alonso, Chem. Commun., 2002, 426;
J.-M. Lee, H.-S. Lim and S.-K. Chung, Tetrahedron: Asymmetry, 2002,
13, 343; R. J. B. H. N. van den Berg, C. G. N. Korevaar, G. A. van der
Marel, H. S. Overkleeft and J. H. van Boom, Tetrahedron Lett., 2002,
43, 8409; T. Murakami and K. Furusawa, Tetrahedron, 2002, 58, 9257;
H. K. Lee, E.-K. Kim and C. S. Pak, Tetrahedron Lett., 2002, 43, 9641;
S. Raghavan, A. Rajender and J. S. Yadav, Tetrahedron: Asymmetry,
2003, 14, 2093; S. Raghavan and A. Rajender, J. Org. Chem., 2003, 68,
7094; R. C. So, R. Ndonye, D. P. Izmirian, S. K. Richardson, R. L.
Guerra and A. R. Howell, J. Org. Chem., 2004, 69, 3233; X. Lu, H.-S.
Byun and R. Bittman, J. Org. Chem., 2004, 69, 5433; R. J. B. H. N. van
den Berg, C. G. N. Korevaar, H. S. Overkleeft, G. A. van der Marel and
J. H. van Boom, J. Org. Chem., 2004, 69, 5699; M. Shimizu, H. Ando
and Y. Niwa, Lett. Org. Chem., 2005, 2, 512; W. Lu and R. Bittman,
Tetrahedron Lett., 2005, 46, 1873; V. D. Chaudhari, K. S. A. Kumar
and D. D. Dhavale, Org. Lett., 2005, 7, 5805; M. G. Capdevila, F. Pasi
and C. Trombini, Org. Lett., 2006, 8, 3303; P. Merino, P. Jiminez and T.
Tejero, J. Org. Chem., 2006, 71, 4685; S. Kim, S. Lee, T. Lee, H. Ko and
D. Kim, J. Org. Chem., 2006, 71, 8661; T. Yamamoto, H. Hasegawa, T.
Hakogi and S. Katsumura, Org. Lett., 2006, 8, 5569; V.-T. Pham, J.-E.
Joo, Y.-S. Tian, C.-Y. Oh and W.-H. Ham, Arch. Pharmacol. Res., 2007,
30, 22; M. Lombardo, A. Sharma, S. Gamre and S. Chattopadhyay,
Tetrahedron Lett., 2007, 48, 633; Y. S. Tian, J.-E. Joo, V.-T. Pham, K.-Y.
Lee and W.-H. Ham, Arch. Pharmacol. Res., 2007, 30, 167; A. S. Kale,
P. S. Sakle, V. K. Gumaste, A. Rakeeb and A. S. Deshmukh, Synthesis,
2007, 2631; H. Yang and L. S. Liebeskind, Org. Lett., 2007, 9, 2993.
7 For the asymmetric synthesis of sphinganine and/or sphingosine see:
E. J. Corey and S. Choi, Tetrahedron Lett., 2000, 41, 2765; B. Olofsson
and P. Somfai, J. Org. Chem., 2003, 68, 2514; S. Torssell and P. Somfai,
Org. Biomol. Chem., 2004, 2, 1643; J. Kobayashi, M. Nakamura, Y.
Mori, Y. Yamashita and S. Kobayashi, J. Am. Chem. Soc., 2004, 126,
9192; D. Enders and A. Mu¨ller-Hu¨wen, Eur. J. Org. Chem., 2004, 1732;
W. Disadee and T. Ishikawa, J. Org. Chem., 2005, 70, 9399; D. Enders,
J. Palecˇek and C. Grondal, Chem. Commun., 2006, 655; Y. Cai, C.-C.
Ling and D. R. Bundle, Org. Biomol. Chem., 2006, 4, 1140; G. Righi,
S. Ciambrone, C. D’Achille, A. Leonelli and C. Bonini, Tetrahedron,
2006, 62, 11821.
◦
>98% de); mp 83–85 C (CHCl3–pentane); [a]2D2 +6.6 (c 0.9 in
CHCl3); {lit.27 [a]D24 +4.3 (c 0.9 in CHCl3)}; mmax (KBr) 3336, 2926,
2851, 1734, 1655, 1539, 1236; dH (400 MHz, CDCl3) 0.88 (3H, t, J
6.8, C(18)H3), 1.14–1.43 (22H, m, C(7)H2-C(17)H2), 1.99 (3H, s,
COMe), 2.05 (3H, s, COMe), 2.08 (3H, s, COMe), 2.00–2.27 (2H,
m, C(6)H2), 4.04 (1H, dd, J 11.6, 3.9, C(1)HA), 4.34 (1H, dd, J
11.6, 6.5, C(1)HB), 4.39–4.47 (1H, m, C(2)H), 5.28–5.36 (1H, m,
C(3)H), 5.60–5.73 (2H, m, C(4)H, C(5)H); dC (125 MHz, CDCl3)
14.1, 20.8, 21.1, 22.7, 23.4, 28.0, 29.3, 29.35, 29.42, 29.5, 29.6,
29.64, 29.66, 29.67, 31.9, 51.1, 62.6, 69.6, 77.2, 123.8, 137.0, 169.8,
170.0, 171.0; m/z (ESI+) 448 ([M + Na]+, 100%); HRMS (ESI+)
C24H43NNaO5 ([M + Na]+) requires 448.3033; found 448.3030.
+
(2S,3R,4E)-1,3-Diacetoxy-2-acetamido-octadec-4-ene
[N,O,O-triacetyl sphingosine] 56
3 M aq HCl (1 mL) was added to a solution of (E)-52 (50 mg,
0.05 mmol, (E) : (Z) 94 : 6) in MeOH (10 mL) and heated at
50 ◦C for 3 h. The reaction mixture was concentrated in vacuo.
The residue was dissolved in pyridine (10 mL) and Ac2O (0.1 mL,
excess) and DMAP (2 mg) were added sequentially. The reaction
mixture was stirred for 12 h before being quenched with H2O
(2 mL). The reaction mixture was diluted with H2O (10 mL) and
Et2O (10 mL) and the layers were separated. The aqueous layer
was extracted with Et2O (2 × 10 mL). The combined organic
layers were washed sequentially with sat aq CuSO4 (2 × 10 mL),
H2O (10 mL) and brine (10 mL), dried and concentrated in vacuo.
Recrystallisation from CHCl3–pentane (1 :◦1) gave 56 as a white
solid (29 mg, 80%, >98% de); mp 99–101 C (CHCl3–pentane);
[a]D20 −12.0 (c 1.0 in CHCl3); {lit.28 [a]D24 −13.0 (c 1.6 in CHCl3)};
mmax (KBr) 3287, 2919, 2850, 1734, 1656, 1552, 1232; dH (400 MHz,
CDCl3) 0.88 (3H, t, J 6.8, C(18)H3), 1.19–1.40 (22H, m, C(7)-
C(17)H2), 1.95–2.09 (2H, m, C(6)H2) overlapping 1.99 (3H, s,
COMe) and 2.07 (6H, s, 2 × COMe), 4.04 (1H, dd, J 11.6, 4.1,
C(1)HA), 4.30 (1H, dd, J 11.6, 6.1, C(1)HB), 4.39–4.48 (1H, m,
C(2)H), 5.26–5.28 (1H, m, C(3)H), 5.39 (1H, dd, J 15.4, 7.5,
C(4)H), 5.68 (1H, d, J 9.2, NH), 5.79 (1H, dd, J 15.4, 6.8,
C(5)H); dC (100 MHz, CDCl3) 14.1, 20.8, 21.1, 22.7, 23.4, 28.9,
29.2, 29.3, 29.4, 29.6, 29.7, 31.9, 32.3, 50.6, 60.4, 62.6, 73.8, 124.1,
137.5, 169.7, 170.0, 171.0; m/z (ESI+) 448 ([M + Na]+, 100%);
8 For a review see: S. G. Davies, A. D. Smith and P. D. Price, Tetrahedron:
Asymmetry, 2005, 16, 2833.
9 M. E. Bunnage, A. N. Chernega, S. G. Davies and C. J. Goodwin,
J. Chem. Soc., Perkin Trans. 1, 1994, 2373.
10 (a) M. E. Bunnage, S. G. Davies and C. J. Goodwin, Synlett, 1993, 731;
M. E. Bunnage, S. G. Davies and C. J. Goodwin, J. Chem. Soc., Perkin
Trans. 1, 1993, 1375; (b) M. E. Bunnage, A. J. Burke, S. G. Davies
and C. J. Goodwin, Tetrahedron: Asymmetry, 1994, 5, 203; (c) M. E.
Bunnage, S. G. Davies and C. J. Goodwin, J. Chem. Soc., Perkin Trans.
1, 1994, 2385; (d) M. E. Bunnage, A. J. Burke, S. G. Davies and C. J.
Goodwin, Tetrahedron: Asymmetry, 1995, 6, 165; (e) A. J. Burke, S. G.
Davies and C. J. R. Hedgecock, Synlett, 1996, 621; (f) M. E. Bunnage,
A. J. Burke, S. G. Davies, N. L. Millican, R. L. Nicholson, P. M. Roberts
and A. D. Smith, Org. Biomol. Chem., 2003, 1, 3708; (g) S. G. Davies,
D. G. Hughes, R. L. Nicholson, A. D. Smith and A. J. Wright, Org.
Biomol. Chem., 2004, 2, 1549.
HRMS (ESI+) C24H43NNaO5 ([M + Na]+) requires 448.3033;
11 E. Abraham, J. I. Candela-Lena, S. G. Davies, M. Georgiou, R. L.
Nicholson, P. M. Roberts, A. J. Russell, E. M. Sa´nchez-Ferna´ndez,
A. D. Smith and J. E. Thomson, Tetrahedron: Asymmetry, 2007, 18,
2510.
+
found 448.3023.
12 M. Ichihashi and K. Mori, Biosci., Biotechnol., Biochem., 2002, 67, 329.
13 The reaction diastereoselectivity was assessed by peak integration of
the 1H NMR spectrum of the crude reaction mixture.
References
1 S. C. Bergmeier, Tetrahedron, 2000, 56, 2561.
14 The ee of 12 was determined by derivatisation with both homochiral
and racemic Mosher’s acid chloride, and subsequent analysis of the
resultant esters by 1H and 19F NMR spectroscopy; see J. A. Dale, D. L.
Dull and H. S. Mosher, J. Org. Chem., 1969, 34, 2543.
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17 S. G. Davies, A. W. Mulvaney, A. J. Russell and A. D. Smith,
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and S. K. Richardson, Tetrahedron, 2004, 60, 11327. For a review of the
synthesis of sphingosine see: P. M. Koskinen and A. M. P. Koskinen,
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