6072
Y. Fall et al. / Tetrahedron Letters 44 (2003) 6069–6072
logues of the vitamin D side chain. Work is in progress
on the synthesis of the corresponding vitamin D’s and
their modification by means of the Ramberg–Ba¨cklund
rearrangement.
Chem. Lett. 1993, 3, 1859–1862; (e) Grue-Sorensen, G.;
Pedersen, H.; Binderup, E. T.; Tranholm, M. PCT Int.
Appl. WO 0156981, 2001, 50 pp.
6. Schmittberger, T.; Uguen, D. Tetrahedron Lett. 1996, 37,
29–32.
7. (a) Leyes, G. A.; Okamura, W. H. J. Am. Chem. Soc.
1982, 104, 6099–6105; (b) Sardina, F. J.; Mourin˜o, A.;
Castedo, L. J. Org. Chem. 1986, 51, 1264–1269.
8. All new compounds exhibited satisfactory 1H and 13C
NMR, analytical, and/or high-resolution mass spectral
data.
9. Braga, A. L.; Appelt, H. R.; Schneider, P. H.; Silveira, C.
C.; Wessjohann, L. A. Tetrahedron: Asymmetry 1999, 10,
1733–1738. For other reducing conditions, see: (b) Barlu-
enga, J.; Rubiera, C.; Fernandez, J. R.; Yus, M. J. Chem.
Soc., Chem. Commun. 1987, 6, 425–426; (c) Ramon, D. J.;
Yus, M. Tetrahedron Lett. 1990, 31, 3763–3766; (d) Fujii,
T.; Ohba, M.; Hatakeyama, H. Chem. Pharm. Bull. 1985,
33, 2355–2359.
Acknowledgements
This work was supported by grants from the Xunta de
Galicia (PGIDT01PXI30105PR) and the Vicerectorate
for Research of the University of Vigo, and by a grant
to O.D. by the Spanish Ministry of Foreign Affairs
(MAE). We also thank Professor D. Uguen of the
University of Strasbourg for supplying us with useful
unpublished experimental details; Solvay Pharmaceuti-
cals (Weesp, The Netherlands) for the gift of starting
materials; and the NMR service of the CACTI, Univer-
sity of Vigo, for NMR studies.
10. Andrews, D. R.; Barton, D. H. R.; Hesse, R. H.; Pechet,
M. M. J. Org. Chem. 1986, 51, 4819–4828.
References
11. Reduction and in situ alkylation of thioacetate 14, typical
procedure (entry 4): To a solution of 14 (200 mg, 0.52
mmol) and sodium hydroxide (41 mg, 1.04 mmol, 2
equiv.) in dry ethanol (5 mL) under an argon atmosphere
(baloon), solid sodium borohydride (42.28 mg, 1.12
mmol, 2.15 equiv.) was added in one portion, by quickly
opening the septum and the mixture was stirred for 30
min at room temperature. tert-Butyl bromoacetate 21
(154 ml, 1.04 mmol, 2 equiv.) was added neat by injection
via syringe through the rubber septum and the resulting
mixture was stirred at room temperature for 1 h. The
ethanol was rotatory evaporated and the residue dis-
solved in dichloromethane (15 mL), washed with water
(2×10 ml), and dried over sodium sulphate. Filtration and
solvent evaporation afforded a residue which was purified
by column chromatography on silicagel (EtOAc/hexane,
10:80) to give 22 in 92% yield as an oil. Selected analyti-
1. Bouillon, R.; Okamura, W. H.; Norman, A. W. Endocr.
Rev. 1995, 16, 200–257.
2. For general reviews of vitamin D chemistry and biology,
see: (a) Vitamin D: Chemistry, Biology and Clinical Appli-
cations of the Steroid Hormone; Norman, A. W.; Bouil-
lon, R.; Thomasset, M., Eds.; Vitamin D Workshop, Inc.:
Riverside, CA, 1997; (b) Feldman, D.; Glorieux, F. H.;
Pike, J. W. Vitamin D; Academic Press: San Diego, 1997;
(c) Dai, H.; Posner, G. H. Synthesis 1994, 1383–1398; (d)
Zhu, G.-D.; Okamura. W. H. Chem. Rev. 1995, 95,
1877–1952.
3. (a) Binderup, L.; Bramm, E. Biochem. Pharmacol. 1988,
37, 889–895; (b) Chen, T. C.; Parsons, K.; Uskokovic, M.
R.; Horst, R. L.; Holick, M. F. J. Nutr. Biochem. 1993, 4,
49–57; (c) Oikawa, T.; Yoshida, Y.; Shimamura, M.;
Ashino-Fuse, H.; Iwaguchi, T.; Tominaga, T. Anticancer
Drugs 1991, 2, 475–480; (d) Abe, J.; Nakano, T.; Nishii,
Y.; Matsumoto, T.; Ogata, E.; Ikeda, K. Endocrinology
1991, 129, 832–837; (e) Abe-Hashimoto, J.; Kikuchi, T.;
Matsumoto, T.; Nishi, Y.; Ogata, E.; Ikeda, K. Cancer
Res. 1993, 53, 2534–2537; (f) Abe, J.; Takita, Y.;
Nakano, T.; Miyaura, C.; Suda, T.; Nishii, Y.
Endocrinology 1989, 124, 2645–2647.
4. (a) Fall, Y. Tetrahedron Lett. 1997, 38, 4909–4912; (b)
Fall, Y.; Gonza´lez, V.; Vidal, B.; Mourin˜o, A. Tetra-
hedron Lett. 2002, 43, 427–429; (c) Fall, Y.; Bolan˜o, T.;
Ferna´ndez, C.; Go´mez, G.; Moma´n, E., manuscript in
preparation.
5. (a) Hesse, R. Eur. Pat. Appl. EP 78704, 1983, 75 pp; (b)
Kubodera, N.; Miyamoto, K.; Akiyama, M.; Mat-
sumoto, M.; Mori, T. Chem. Pharm. Bull. 1991, 39,
3221–3224; (c) Calverly, M. J.; Grue-Soerensen, G.;
Binderup, E. T. PCT Int. Appl. WO 9115475, 1991, 64
pp; (d) Allewaert, K.; Van Baelen, H.; Bouillon, R.;
Zhao, X. Y.; De Clercq, P.; Vandewalle, M. Bioorg. Med.
1
cal data for 22: H NMR (300 MHz, CDCl3): l 4.01 (1H,
br s, CH-8), 3.10 (1H, d, J=14.3, CH-24a), 3.03 (1H, d,
J=14.3, CH-24b), 2.81 (1H, dd, J=12.3, 2.7, CH-22a),
2.34 (1H, dd, J=12.3, 8.8, CH-22b), 1.48 (9H, s, OtBu),
1.05 (3H, d, J=6.5, CH3-21), 0.92 (3H, s, CH3-18), 0.89
(9H, s, tBuSi), 0.01 (3H, s, MeSi), 0.00 (3H, s, MeSi); 13C
NMR (CDCl3): l 170.21 (C), 81.56 (C), 69.73 (C-8),
56.38, 53.29, 42.71 (C), 40.80 (CH2), 40.47 (CH2), 36.15,
35.96 (CH2), 34.75 (CH2), 28.36 (OtBu), 27.57 (CH2),
26.18 (tBuSi), 23.40 (CH2), 19.05, 18.37 (C), 17.98 (CH2),
14.15, −4.42 (MeSi), −4.79 (MeSi); MS (m/e): 456 (M+,
9%), 401 (49%), 399 (16%), 355 (9%), 343 (14%), 309
(12%), 269 (42%), 267 (18%), 209 (14%), 177 (100%).
12. (a) Paquette, L. Org. React. 1970, 25, 1–71; (b) Chan,
T.-L.; Fong, S.; Li, Y.; Man, T.-O.; Poon, C.-D. J. Chem.
Soc., Chem. Commun. 1994, 1771–1772; (c) Vanda, C.;
Giuseppe, M.; Francesca, P.; Salvatore, P.; Alfredo, R.
Tetrahedron 2000, 56, 1225–1231; (d) Schmittberger, T.;
Uguen, D. Tetrahedron Lett. 1997, 38, 2837–2840.