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Vitamin D


DATA No : VVD0121 INFORMANT : Sachiko Yamada

NAME : (5Z,7E,22E)-(1S,3R,24S)-26,27-cyclo-9,10-seco-5,7,10(19),22-cholestatetraene-1,3,24-triol

COMMON NAME: (22E)-(24S)-1a,24-dihydroxy-26,27-cyclo-22,23-didehydrovitamin D3 / (22E)-(24S)-1a,24-dihydroxy-26,27-cyclo-22,23-didehydrocholecalciferol / Calcipotriol
SYMBOL: (22E)-1a,24S-(OH)2-26,27-cyclo-22,23-didehydro-D3
FORMULA: C27H40O3 MOL.WT (average) : 412.605


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BIOLOGICAL ACTIVITY
Activity relative to 1,25-(OH)2D3 (defined 100%) : Affinity for the receptor in U937 cells (human histiocytic lymphoma cell line) : 200 ; Antiproliferative effects on U937 cells : 200 ; Induction of differentiation of U937 cells : 100 ; Calciuric effect: <0.5. (Ref. 0309)
This compound named calcipotriol (Leo laboratory code MC903) is the first active vitamin D analog to receive governmental approval to be used as an anti-proliferative agent in the treatment of psoriasis. (Ref. 0327)
PHYSICAL AND CHEMICAL PROPERTIES
MELTING POINT:(Methyl formate) 166-158 degC (Ref. 0289)

BOILING POINT:

REFRACTIVE INDEX:

OPTICAL ROTATION:

DENSITY:

SOLUBILITY:
SPECTRAL DATA
UV SPECTRA:lmax (nm) (e) 264 (17200) (Ref. 0289)

IR SPECTRA:

NMR SPECTRA:1H-NMR (d, CDCl3) 0.15-0.65 (4H, m), 0.56 (3H, s), 0.75-1.10 (1H, m), 1.05 (3H, d, J = 7.0 Hz), 3.45 (1H, m), 4.2 (1H, m), 4.4 (1H, m), 4.99 (1H, m), 5.31 (1H, m), 5.47 (2H, m), 5.99 (1H, d, J = 11.0 Hz), 6.36 (1H, d, J = 11.0 Hz) (Ref. 0289)

MASS SPECTRA:m/z 412 (M+, 6), 394 (8), 379 (2), 376 (5), 287 (5), 285 (7), 283 (8), 269 (11), 267 (6), 265 (4), 251 (12), 152 (26), 134 (100) (Ref. 0289)

OTHER SPECTRA:
CHROMATOGRAM DATA

SOURCE

CHEMICAL SYNTHESIS
From protected (5E)-1a-hydroxy-22-oxo-23,24,25,26,27-pentanorvitamin D3 via Wittig-Horner coupling with side chain fragment, reduction, separation of 24-epimers, photochemical isomerization and deprotection. (Ref. 0289)
METABOLISM
The in vitro metabolism of the title compound (calcipotriol) was studied in two keratinocyte cell models. Calcipotriol was initially converted into the 24-ketone and its 22,23-dihydro-derivative. Further metabolites such as two 23-epimeric 23-hydroxylated 22,23-dihydro-24-oxo-derivatives, two 23,24-dihydroxy-derivatives and side chain-cleavage products, tetranor-1,23-(OH)2D3 and calcitroic acid. (Ref. 0322)
GENETIC INFORMATION

NOTE

REFERENCES
[0289]
AUTHOR:Calverley, M. J.
TITLE:Synthesis of MC 903, A Biologically Active Vitamin D Metabolite Analogue.
JOURNAL:Tetrahedron
VOL:43 PAGE : 4609 -4619 (1987)
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[0309]
AUTHOR:Binderup, L., and Bramm, E.
TITLE:Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo PubMed ID:2830885
JOURNAL:Biochem Pharmacol.
VOL:37 PAGE : 889-895 (1988)
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[0322]
AUTHOR:Masuda, S., Strugnell, S., Calverley, M. J., Makin, H. L., Kremer, R., and Jones, G.
TITLE:In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models PubMed ID:8106449
JOURNAL:J Biol Chem.
VOL:269 PAGE : 4794-4803 (1994)
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[0327]
AUTHOR:Kragballe, K., Gjertsen, B. T., De Hoop, D., Karlsmark, T., van de Kerkhof, P. C., Larko, O., Nieboer, C., Roed-Petersen, J., Strand, A., and Tikjob, G.
TITLE:Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris PubMed ID:1670840
JOURNAL:Lancet.
VOL:337 PAGE : 193-196 (1991)
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Last updated June 19, 2007. Copyright © 1989-2007 Japanese Conference on the Biochemistry of Lipids (JCBL). All rights reserved.