3
A.; Szelejewski, W.; Opolski, A. Steroids 2004, 69, 629–635.
(d) Wietrzyk, J.; Nevozhay, D.; Filip, B.; Milczarek, M.; Kutner,
A. Anticancer Res. 2007, 27 (5A), 3387–3398. (e) Wietrzyk, J.;
Nevozhay, D.; Milczarek, M.; Filip, B.; Kutner, A. Cancer
Chemother. Pharmacol. 2008, 62 (5), 787–797. (f) Wietrzyk,
J.; Chodynski, M.; Fitak, H.; Wojdat, E.; Kutner, A.; Opolski, A.
Anticancer Drugs 2007, 18 (4), 447–457.
(a) Morisaki, M.; Koizum, N.; Ikekawa, N.; Takeshita, T.;
Ishimoto, S. J. Chem. Soc., Perkin. Trans. I 1975, 1421-1424.
(b) Koch, P.; Nakatani, Y.; Luu, B.; Ourisson, G. Bull. Soc.
Chim. Fr. 1983, 189-194. (c) Okamoto, M.; Tabe, M.; Fujii, T.;
Tanaka, T. Tetrahedron Asymmetry 1995, 6, 767-778.
(a) Zhang, H.; Guo, W.; Fang, Z. Tetrahedron Asymmetry
2017, 28, 410-413.
Okamoto, M.; Fujii, T.; Tanaka, T. Tetrahedron 1995, 51,
5543-5556.
Oshida, J-I.; Okamoto, M.; Azuma, S.; Tanaka, T. Tetrahedron
Asymmetry 1997, 8, 2579-2584.
Fall, Y.; Torneiro, M.; Castedo, L.; Mouriño, A. Tetrahedron
1997, 53, 4703-4714.
Fall, Y.; Torneiro, M.; Castedo, L.; Mouriño, A. Tetrahedron
Lett. 1992, 33, 6683-6686.
Our strategy to use the modified Julia olefination in the field
of vitamin D is not unprecedented. Indeed Wietrzyk and co-
15
workers as well as Kutner and co-workers16 used it for the
synthesis of calcipotriol and analogues. However as they used
the vitamin D C-22 sulfone to carry out the modified Julia
olefination, their synthesis unfortunately does not allow
access to the corresponding A ring modified analogues,17
some of which are depicted in Figure 2.
3
4
5
6
7
8
9
Figure 2. Structures of tacalcitol and some of its possible A-
ring modified analogues
(a) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron
Lett. 1991, 32, 1175 - 1178. (b) Baudin, J. B.; Hareau, G.; Julia,
S. A.; Lorne, R.; Ruel, O. Bull. Soc. Chim. Fr. 1993, 130, 856 -
We have also to say that we already patented in 2012 a modified
Julia olefination approach for the synthesis of 25-hydroxi-
vitamin D2 side chain.18
878. (c) Blakemore, P. R. J. Chem. Soc. , Perkin Trans. 1 2002
,
2563 - 2585. (d) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.;
Morley, A. Synlett 1998, 1, 26 -28. (e) Kocienski, P. J.; Bell, A.;
Blakemore, P. R. Synlett 2000, 3, 365 - 366. (f) Sorg, A. ;
Brückner, R. Synlett 2005, 2, 289 - 293. (g) Vaz, B. ; Alvarez,
R. ; Souto, J. A. ; de Lera, A. R. Synlett 2005, 2, 294 – 298.
Conclusion
10 (a) Leyes, G. A.; Okamura, W. H. J. Am. Chem. Soc. 1982, 104,
6099-6105. (b) ) Sardina, F.; Mouriño, A.; Castedo, L. J. Org.
Chem. 1986, 51, 1264-1269.
11 (a) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M.
Tetrahedron Lett. 2003, 44, 8293-8296. (b) List, B. J. Am.
Chem. Soc. 2002, 124, 5656-5657. (c) Brown, S. P.; Brochu,
In summary, we have developed a new and convergent
synthesis of tacalcitol which will pave the way to
unprecedented
A
ring modified analogues of this
commercially available drug used as treatment for psoriasis.
M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003
125, 10808-10809. (d) Zhong, G. Angew. Chem. Int. Ed. 2003
,
,
42, 4247-4250. (e) Córdova, A.; Sundén, H.; Bogeviig, A.;
Johanson, M.; Himo, F. Chem. Europ. J. 2004, 10, 3673-3684
(f) Gharpure, S. J.; Nanda, L. N.; Shukla, M. K. Eur. J. Org.
Chem. 2011, 6632-6635.
Acknowledgements
This work was supported financially by the Xunta de Galicia
(CN 2012/184). The work of the NMR and MS divisions of
the research support services of the University of Vigo
(CACTI) is also gratefully acknowledged. A. M. thanks the
University of Vigo for a fellowship.
12 (a) Schenk, S; Weston, J.; Anders, E. J. Am. Chem. Soc. 2005
,
127, 12566-12576. (b) Ono, K.; Yoshida, A.; Saito, N.;
Fujishima, T.; Honzawa, S.; Suhara, Y.; Kishimoto, S.; Sugiura,
T.; Waku, K.; Takayama, H.; Kittaka, A. J. Org. Chem. 2003, 68,
7407-7415. (c) Mitsunobu, O. Synthesis 1981, 1-28. (d)
Mitsunobu, O.; Kato, K. J. Org. Chem. 1970, 35, 4227-4229.
13 Poterala, M.; Plenkiewicz, J. Tetrahedron Asymmetry 2011
22, 294-299.
,
References and notes
14 (a) Mouriño, A; Torneiro, M.; Vitale, C.; Fernández, S.; Perez-
Sestelo, J.; Anne, S.; Gregorio, C. Tetrahedron Lett. 1997, 33,
4713-4716. (b) Daniewski, A. R.; Garofalo, L. M.; Hutchings, S.
D.; Kabat, M. M.; Liu, W.; Okabe, M., Radinov, R.; Yiannikour,
G. P. J. Org. Chem. 2002, 67, 1580-1587.
15 Milczarek, M.; Chodynski, M., Filip-Psurska, B.; Martowicz, A.;
Krupa, M.; Krajewski, K.; Kutner, A.; Wietrzyk, J. Cancers
2013, 5, 1355-1378.
16 Pietraszek, A.; Malinska, M.; Chodynski, M.; Martynow, J.;
Krupa, M.; Maruszak, W.; Wozniak, K.; Kutner, A. J. Pharm.
Sci. 2013, 102, 3925-3931.
17 For a review on A-ring modified analogues of calcitriol, see:
Glebocka, A; Chiellini, G. Arch. Biochem. Biophys. 2012, 523,
48-57.
1
For the most recent total synthesis of calcitriol see: (a) López-
Pérez, B.; Maestro, M. A.; Mouriño, A. Chem. Commun, 2017
,
53, 8144-8147. For general reviews on the chemistry and/or
biochemistry of vitamin D, see: (b) Vitamin D: Chemistry,
Biology and Clinical Applications of the Steroid Hormone;
Norman, A. W., Bouillon, R., Thomasset, M., Eds; Vitamin D
Workshop, Inc.: Riverside, CA, 1997. (c) Feldman, D.;
Glorieux, F. H.; Pike, J. W. Vitamin D; Academic Press: San
Diego, 1997. (d) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr.
1985, 98-114. (e) Dai, H.; Posner, G. H. Synthesis 1994, 1383-
1398. (f) Zhu, G.-D., Okamura. W. H. Chem. Rev. 1995, 95,
1877-1952. (g) Posner, G. H.; Kahraman, M. Eur. J. Org.
Chem. 2003, 3889-3895.
18 Fall, Y. et al. Spanish Patent ES 2380477B2
2
(a) Opolski, A.; Wietrzyk, J.; Chrobak, A.; Marcinkowska, E.;
Wojdat, E.; Kutner, A.; Radzikowski, C. Anticancer Res. 1999,
19 (6B), 5217–5222. (b) Opolski, A.; Wietrzyk, J.; Siwinska, A.;
Marcinkowska, E.; Chrobak, A., Radzikowski, C.; Kutner, A.
Curr. Pharm. Des. 2000, 6 (7), 755–765. (c) Wietrzyk, J.;
Pelczynska, M.; Madej, J.; Dzimira, S.; Kusnierczyk, H., Kutner,