Design and synthesis of active vitamin D analogs

Journal of Steroid Biochemistry and Molecular Biology

Volumn 121, Issue 1-2, 2010, Pages 7-12

  Eduardo Canosa, Silvina ^a   Fraga, Ramón ^a   Sigüeiro, Rita ^a   Marco, Maria ^a   Rochel, Natacha ^b   Moras, Dino ^b   Mouriño, Antonio ^a  

^a UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^b INSTITUT DE GÉNÉTIQUE ET DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

Author keywords

Aromatic seco steroidal D ring; Design; Docking; Structure; Synthesis; Vitamin D3 analogs

Indexed keywords

AROMATIC COMPOUND; BENZENE DERIVATIVE; CALCITRIOL; VITAMIN D DERIVATIVE; BENZENE; CALCITRIOL RECEPTOR; CARBON; VITAMIN D;

ARTICLE; BIOLOGICAL ACTIVITY; CATALYSIS; CYCLIZATION; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; MOLECULAR DOCKING; RING CLOSING METATHESIS; STRUCTURE ACTIVITY RELATION; ANALOGS AND DERIVATIVES; ANIMAL; APOPTOSIS; BOVINAE; CHEMICAL MODEL; CHEMISTRY; DIMERIZATION; HUMAN; MEDICINAL CHEMISTRY; NEOVASCULARIZATION (PATHOLOGY); PROCEDURES;

ANIMALS; APOPTOSIS; BENZENE; CARBON; CATALYSIS; CATTLE; CHEMISTRY, PHARMACEUTICAL; DIMERIZATION; DRUG DESIGN; HUMANS; MODELS, CHEMICAL; NEOVASCULARIZATION, PATHOLOGIC; RECEPTORS, CALCITRIOL; STRUCTURE-ACTIVITY RELATIONSHIP; VITAMIN D;

EID: 77954763363     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2010.03.036     Document Type: Article

References (71)

1. The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, which dimerized with the retinoid X receptor (RXR). These heterodimers binds the vitamin D response elements (VDREs.) in target gene promoters and recruit coactivator proteins to modulate target gene transcription.
2. Evans R.M. The steroid and thyroid hormone receptor superfamily. Science 1988, 240:889-895.
3. 3 signalling. Nature 1992, 355:446-449.
4. Laudet V., Gronemeyer H. The Nuclear Receptor Facts Book 2002, Academic Press, London.
5. Norman A.W. Vitamin D the Calcium Homeostatic Steroid Hormone 1979, Academic Press, New York.
6. Tanaka H., Abe E., Miyaura C., Kuribayashi T., Cono K., Nishii Y., Suda T. 1α,25-Dihydroxycholecalciferol and human myeloid cell line (HL-60). Biochem. J. 1982, 204:713-771.
7. 3. Proc. Natl. Acad. Sci. U.S.A. 1981, 78:4990-4994.
8. 3. J. Cell. Biochem. 1992, 49:26-31.
9. Jones G., Strugnell S.A., DeLuca H.F. Physiol. Rev. 1998, 78:1193-1231.
10. Vitamin D 2005, Academic Press, New York. D. Feldman, F.H. Glorieoux, J.W. Pike (Eds.).
11. Dusso A.S., Brown A.J., Slatopolsky E. Vitamin D. Am. J. Physiol. Renal Physiol. 2005, 289:F8-F28.
12. R. Bouillon, A.W. Norman, J.R. Pasqualini (Eds.), Proceedings of the 12th Workshop on Vitamin D, J. Steroid Biochem. Mol. Biol. 89-90 (2004) 1-633, and the previous 11 volumes in this series.
13. R. Bouillon, A.W. Norman, J.R. Pasqualini (Eds.), Proceedings of the 13th Workshop on Vitamin D. J. Steroid Biochem. Mol. Biol. 103 (2007) 201-822.
14. Bouillon R., Okamura W.H., Norman A.W. Structure-function relationships in the vitamin D endrocrine system. Endocr. Rev. 1995, 16:200-257.
15. Banerjee P., Chatterjee M. Antiproliferative role of vitamin D and its analogs-a brief overview. Mol. Cell. Biochem. 2003, 253:247-254.
16. Campbell M.J., Adorini L. The vitamin D receptor as a therapeutic target. Expert Opin. Ther. Targets 2006, 10:735-748.
17. Holick M.F. Vitamin D: a millennium perspective. J. Cell. Biochem. 2003, 88:296-307.
18. Bouillon R., Eelen G., Verlinden L., Mathieu C., Carmeliet G., Verstuyf A. Vitamin D and cancer. J. Steroid Biochem. Mol. Biol. 2006, 102:156-162.
19. Ebert R., Schütze N., Adamski J., Jakob F. Vitamin D signaling is nodulated on multiple levels in health and disease. Mol. Cell. Endocrinol. 2006, 248:149-159.
20. Fraser D., Kooh S.W., Kina H.P., Holick M.F., Tanaka Y., DeLuca H.F. Pathogenesis of hereditary vitamin D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1α,25-dihydroxyvitamin D. N. Engl. J. Med. 1973, 89:817-822.
21. Glorieux F.H., Marie P.J., Pettifor J.M., Delvin E.E. Bone response to phosphate salts, ergocalciferol, and calcitriol in hypophosphatemic vitamin D-resistant rickets. N. Engl. J. Med. 1980, 303:1023-1031.
22. Slatopolski E.S., Brown A.J. Vitamin D and Renal Failure, in Vitamin D 1997, 849-865. Academia Press, San Diego, CA. D. Feldman, F.H. Glorieux, J.W. Pike (Eds.).
23. Drezner M.K. Clinical Disorders of Phosphate Homeostasis, Vitamin D 1997, 733-753. Academia Press, San Diego, CA. D. Feldman, F.H. Glorieux, J.W. Pike (Eds.).
24. Lamberg-Allardt C. Is there a role for vitamin D in osteoporosis?. Calcified Tissue Int. 1991, 49:S46-S49.
25. Langner A., Verjans H., Stapo V., Mol M., Fraczykowska M. Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study. Br. J. Dermatol. 1993, 128:566-571.
26. Hayes C.E. Vitamin D: a natural inhibitor of multiple sclerosis. Proc. Nutr. Soc. 2000, 59:531-535.
27. Konety B.R., Getzenberg R.H. Vitamin D and prostate cancer. Urol. Clin. North Am. 2002, 29:95-106.
28. 3 on breast cells: a mini review. Braz. J. Med. Biol. Res. 2002, 35:1-9.
29. Ettinger R.A., DeLuca H.F. The vitamin D endocrine system and its therapeutical potential. Adv. Drug Res. 1996, 28:269-312.
30. Stein M.S., Wark D.L. An update on the therapeutic potential of the vitamin D analogues. Expert Opin. Invest. Drugs 2003, 12:825-840.
31. Debb K.K., Trump D.L., Jonson C.S. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat. Rev. Cancer 2007, 7:684-700.
32. A large number of synthesized analogs are modified at the side-chain, the most flexible and synthetically accessible part of the 1α,25(OH)2D3 skeleton:.
33. Kabat M.M., Radinov R. Curr. Opin. Drug Discov. Dev. 2001, 4:808-833.
34. Brown A.J. Am. J. Kidney Dis. 2001, 3:S3-S19.
35. Carlberg C., Mouriño A. New vitamin D receptor ligands. Expert Opin. Ther. Patents 2003, 13:761-772.
36. Calverley M.J. Synthesis of MC-903, a biologically active vitamin D metabolite analogue. Tetrahedron 1988, 43:4609-4619.
37. Binderup L., Kragballe K. Origin of the use of calcipotriol in psoriasis treatment. Rev. Contemp. Pharmacother. 1992, 3:357-365.
38. Okamura W.H., Norman A.W., Wing R.M. Vitamin D: concerning the relationship between molecular topology and biological function. Proc. Natl. Acad. Sci. U.S.A. 1974, 71:4194-4197.
39. 3. Science 1974, 186:939-941.
40. 2. J. Org. Chem. 1978, 43:1653-1656.
41. Suwinska K., Kutner A. Crystal and molecular structure of 1,25-dihydroxycholecalciferol. Acta Crystallogr. 1996, B52:550-554.
42. 3, a novel vitamin D-related compound with potential therapeutic activity. Tetrahedron Lett. 1990, 31:1823-1824.
43. 3. Tetrahedron Lett. 1992, 33:5445-5448.
44. 3. J. Bone Miner. Res. 1993, 8:1009-1015.
45. Okamura W.H., Palenzuela J.A., Plumet J., Middland M.M. Vitamin D: structure-function analysis and the design of analogs. J. Cell. Biochem. 1992, 49:10-18.
46. Midland M.M., Plumet J., Okamura W.H. Effect of C20 stereochemistry on the conformational profile of the side chains of vitamin D analogs. Biomed. Chem. Lett. 1993, 3:1799-1804.
47. Yamada S., Yamamoto K., Masuno H., Ohta M. Conformation-function relationship of vitamin D: conformational analysis predicts potential side-chain structure. J. Med. Chem. 1998, 41:1467-1475.
48. Okamura W.H., Midland M.M., Hill D.K., Ringe K., Takeuchi J.A., Vassar V.C., Vu T.H., Zhu G.-D., Norman A.W., Bouillon R., Farach-Carson M.C. Vitamin D, Chemistry, Biology and Clinical Applications of the Steroid Hormone, 1997, 11-18. Vitamin Workshop Inc., University of California, Riverside. W.W. Norman, R. Bouillon, M. Tomasset (Eds.).
49. 3. J. Med. Chem. 1991, 34:2452-2463.
50. 3 analogues with fixed torsion angle C(16-17-20-22). Tetrahedron Lett. 1998, 39:4725-4728.
51. 3). J. Org. Chem. 2000, 65:6978-6983.
52. Calverley M.J., Grue-Soerensen G., Bretting C., Binderup L. Chemistry and biology of highly active 22-oxy analogs of 20-epi-calcitriol with very low binding affinity to the vitamin D receptor. Proceedings of the 9th Workshop on Vitamin D 1994, pp. 85-86.
53. Riveiros R., Rumbo A., Sarandeses L., Mouriño A. Synthesis and conformational analysis of 17α,21-cyclo-22-unsaturated analogues of calcitriol. J. Org. Chem. 2007, 72:5477. For related recent studies see also:.
54. Rochel N., Wurth J.M., Mitschier A., Klaholz B., Moras D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 2000, 5:173-179.
55. 3) induce vitamin D receptor transcriptional activity. Org. Lett. 2003, 5:4033-4036.
56. Calverley M.J. Design, synthesis and testing of a novel calcitriol analogue with an essentially rigid side chain that aligns well with the Moras conformation for the receptor-bound natural ligand. Lecture Presented at 12th Workshop on Vitamin D 2003.
57. Rochel N., Hourai S., Perez-Garcia X., Rumbo A., Mouriño A., Moras D. Crystal structure of the vitamin D nuclear receptor ligand binding domain in complex with a locked side chain analog of calcitriol. Arch. Biochem. Biophys. 2007, 460(2):172-176.
58. 3 analogues with side chain at C12. J. Med. Chem. 2006, 49:1509-1516.
59. Hourai S., Rodrigues L.C., Antony P., Reina-San Martin B., Ciesielski F., Magnier B.C., Schoonjans K., Mouriño A., Rochel N., Moras D. Structure-based design of a superagonist ligand for the vitamin D nuclear receptor. Chem. Biol. 2008, 15:383-392.
60. This strategy is considered one of the best routes to vitamin D analogs because it provides in one step the vitamin D triene unit under mild conditions. This approach presents, however, a few disadvantages namely: (a) the preparation of small quantities of up to 50mg of compound that requires an excess of the phosphine oxide (A-ring fragment); (b) the multistep preparation of the phosphine oxide required for coupling with the upper ketone (CD-side chain fragment), and (c) the low yield obtained in the formation of the triene unit when some C-ring or A-ring substituted fragments are used. For details, see:.
61. Lythgoe B. Synthetic approaches to vitamin D and its relatives. Chem. Soc. Rev. 1980, 9:449-475.
62. Baggiolini E.G., Iacobelli J.A., Hennessy B.M., Batcho A.D., Sereno J.F., Uskokovic M.R. Stereocontrolled total synthesis of 1α,25-dihydroxycholecalciferol and 1α,25-dihydroxyergocalciferol. J. Org. Chem. 1986, 51:3098-3108.
63. This strategy, pioneered by Lythgoe [23a] and improved by Mouriño [24c] and Okamura [24d], uses as the key step a thermal isomerization of a previtamin D to produce the vitamin D triene system through an antarafacial sigmatropic [1,7]-hydrogen shift. Lythgoe's dienyne strategy presents the following advantages: (1) the easy and short preparation of the A-ring enyne (bottom fragment); and (2) the easy preparation of the enol triflate (upper fragment) from the corresponding ketone. The main disadvantages are: (1) the overhydrogenation during Lindlar partial hydrogenation of the triple bond to produce the previtamin D intermediate, (2) the low yield on vitamin D when thermal isomerization favors the previtamin D intermediate, and (3) the instability of the vitamin D under the thermal isomerization.
64. Zhu G.-D., Okamura W.H. Synthesis of vitamin D (calciferol). Chem. Rev. 1995, 95:1877-1952.
65. Dai H., Posner G.H. Synthetic approaches to vitamin D. Synthesis 1994, 1383-1398.
66. Castedo L., Mouriño A., Sarandeses L.A. Palladium-catalyzed synthesis of dienynes related to vitamin D from enol triflates. Tetrahedron Lett. 1986, 27:1523-1526.
67. Aurrecoechea J.M., Okamura W.H. A short, enantiospecific synthesis of the hydroxyvitamin D enyne A-ring synthon. Tetrahedron Lett. 1987, 28:4947-4950.
68. Hammond M.L., Mouriño A., Okamura W.H. Sigmatropic rearrangement of vinylallenes: a novel route to the 1-hydroxyvitamin D system. J. Am. Chem. Soc. 1978, 100:4907-4908. This interesting route to vitamin D analogs is based on the thermal isomerization of a vinyallene triene system to produce the vitamin D triene through a thermal suprafacial [1,5]-sigmatropic hydrogen shift. This approach cannot be applied to the synthesis of analogs that are unstable or easily isomerizes to the corresponding previtamins. The synthetic potential of this route to prepare new vitamin D analogs have not yet been explored. For details, see:.
69. 3 and analogues. Org. Lett. 2005, 7:5885-5887.
70. Cornelius L., Combs D. A convenient synthesis of mono- and polyhalogenated benzocyclanones. Synth. Commun. 1994, 24:2777-2788.
71. Krasovskiy A., Malakhov V., Gavryushin A., Knochel P. Efficient synthesis of functionalized organozinc compounds by the direct insertion of zinc into organic iodides and bromides. Angew. Chem. Int. Ed. 2006, 45:6040-6044.