Synthesis and biological activity of previtamin D(3) analogues with A-ring modifications.
Synthesis of two novel 6-s-cis analogues of 1alpha,25-dihydroxyvitamin D3 are described using shikimic acid and its 4-epi isomer as versatile chiral starting materials. These derivatives contain a 2beta-(3'-hydroxypropoxy) moiety or a 2beta,3beta-epoxy group into 1alpha,25-OH(2)-19-nor-pre-D3. The synthesized analogues were found to be not suitable for binding to the vitamin D receptor and showed weak binding affinity toward the vitamin D-binding protein. The new derivatives failed to inhibit cell proliferation.
Sánchez-Abella
Laura
L
Departamento de Química Orgánica e Inorgánica and Instituto Universitario de Biotecnología de Asturias, Universidad de Oviedo, 33006 Oviedo (Asturias), Spain.
Fernández
Susana
S
Verstuyf
Annemieke
A
Verlinden
Lieve
L
Gotor
Vicente
V
Ferrero
Miguel
M
D002117:Calcitriol / Q000031:analogs & derivatives*; D049109:Cell Proliferation / Q000187:drug effects; D002762:Cholecalciferol / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014809:Vitamin D-Binding Protein / Q000378:metabolism
D014809:Vitamin D-Binding Protein; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002762:Cholecalciferol; D002117:Calcitriol