T. Ayad et al. / Tetrahedron Letters 44 (2003) 579–582
581
Scheme 3. Reagents and conditions: (i) (1S,2S)-1,2-N,N%-bis(trifluoromethanesulfonylamino)cyclohexane (0.05 equiv. for R=
C2H5, 0.2 equiv. for R=C6H13), Ti(Oi-Pr)4 (1.2 equiv.) R2Zn (2.4 equiv. for R=C2H5, 3.5 equiv. for R=C6H13), degassed
toluene, −20°C for R=C2H5, −10°C for R=C6H13, 20 h, 80% (95% de) for R=C2H5, 40% (100% de) for R=C6H13; (ii) NaN3
(5 equiv.), NH4Cl (2 equiv.), methoxyethanol/H2O, 120°C, 5 h, 80% for R=C2H5, 65% BRSM at 80% of conversion for
R=C6H13, C-2/C-3 opening ratio 75/25; (iii) dimethoxypropane, CSA (cat.), rt, overnight, quant.; (iv) (a) Et3N·3HF (4 equiv.),
THF, rt, 24 h, (b) 10% Pd/C (cat.), MeOH, rt, 18 h, (c) Ac2O/pyridine (1/1), rt, 24 h, 90% (three steps) for R=C2H5, 85% (three
steps) for R=C6H13.
ful biological tools.35 Thanks to the mildness of
diorganozinc reagents, this approach opens the way to
the preparation of novel functionalized phytosphin-
gosine analogs.
9. Pettit, G. R.; Xu, J.-P.; Gingrich, D. E.; Williams, M. D.;
Doubek, D. L.; Chapuis, J.-C.; Schmidt, J. M. J. Chem.
Soc., Chem. Commun. 1999, 915–916.
10. Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai,
T.; Sawa, E.; Yamaji, K.; Koezuka, Y.; Kobayashi, E.;
Fukushima, H. J. Med. Chem. 1995, 38, 2176–2187.
11. Nakagawa, R.; Motoki, K.; Ueno, H.; Ijima, R.; Naka-
mura, H.; Kobayashi, E.; Shimosaka, A.; Koezuka, Y.
Cancer Res. 1998, 58, 1202–1207.
Acknowledgements
T.A. thanks the ‘Ministe`re de l’Education Nationale de
la Recherche et des Technologies’ for a grant. We are
grateful to Ste´phane Massou for NMR experiments
and Chantal Zedde for HPLC analyses.
12. Gonzales-Aseguinolaza, G.; de Oliveira, C.; Tomaska,
M.; Hong, S.; Bruna-Romero, O.; Nakayama, T.;
Taniguchi, M.; Bendelac, A.; Van Kaer, L.; Koezuka, Y.;
Tsuji, M. Proc. Natl. Acad. Sci. USA 2000, 97, 8461–
8466.
13. Recent references concerning synthesis of natural
D-ribo-
References
phytosphingosine: (a) Luo, S.-Y.; Thopate, S. R.; Hsu,
C.-Y.; Hung, S.-C. Tetrahedron Lett. 2002, 43, 4889–
4892; (b) He, L.; Byun, H.-S.; Bittman, R. J. Org. Chem.
2000, 65, 7618–7626; (c) Azuma, H.; Tamagaki, S.;
Ogino, K. J. Org. Chem. 2000, 65, 3538–3541; (c) Grazi-
ani, A.; Passacantilli, P.; Piancatelli, G.; Tani, S. Tetra-
hedron: Asymmetry 2000, 11, 3921–3937; (d) Figueroa-
Pe´rez, S.; Schmidt, R. R. Carbohydr. Res. 2000, 328, 95–
102. Recent references concerning unnatural diastereo-
mers: (d) Ndakala, A. J.; Hashemzadeh, M.; So, R. C.;
Howell, A. R. Org. Lett. 2002, 4, 1719–1722; (e) Naka-
mura, T.; Shiozaki, M. Tetrahedron 2001, 57, 9087–9092;
(f) Fernandes, R. A.; Kumar, P. Tetrahedron Lett. 2000,
41, 10309–10312.
1. Recent reviews of metabolism and biological functions of
sphingolipids: (a) Hannun, Y. A.; Luberto, C.; Argraves,
K. M. Biochemistry 2001, 40, 4893–4903; (b) Huwiler, A.;
Kolter, T.; Pfeilschifter, J.; Sandhoff, K. Biochim. Bio-
phys. Acta 2000, 1485, 63–99.
2. Zellner, J. Monatsh. Chem. 1911, 32, 133–142.
3. Reindel, F. Annalen 1930, 480, 76–92.
4. Carter, H. E.; Celmer, W. D.; Lands, W. E. M.; Mueller,
K. L.; Tomizawa, H. H. J. Biol. Chem. 1954, 204, 613–
623.
5. For their abundance in skin, see: (a) Wertz, P. W.;
Swartzendruber, D. C.; Madison, K. C.; Downing, D. T.
J. Invest. Dermatol. 1987, 89, 419–425. For their role in
the epidermal water permeability barrier, see: (b) Land-
mann, L. Anat. Embryol. 1988, 178, 1–13.
14. Recent references concerning structural variations in the
sphingosine and sphinganine series: (a) Chun, J.; He, L.;
Byun, H.-S.; Bittman, R. J. Org. Chem. 2000, 65, 7634–
7640; (b) Van Overmeire, I.; Boldin, S. A.; Venkatara-
man, K.; Zisling, R.; De Jonghe, S.; Van Calenbergh, S.;
De Keukeleire, D.; Futerman, A. H.; Herdewijn, P. J.
Med. Chem. 2000, 43, 4189–4199.
6. Wells, G. B.; Dickson, R. C.; Lester, R. L. J. Biol. Chem.
1998, 273, 7235–7243.
7. Zanolari, B.; Friant, S.; Funato, K.; Sutterlin, C.; Steven-
son, B. J.; Riezman, H. EMBO J. 2000, 19, 2824–2833.
8. Inagaki, M.; Isobe, R.; Kawano, Y.; Miyamoto, T.;
Komori, T.; Higuchi, R. Eur. J. Org. Chem. 1998, 129–
131.
15. Guanti, G.; Banfi, L.; Narisano, E. Tetrahedron Lett.
1989, 30, 5507–5510.