A concise and efficient route to 2alpha-(omega-hydroxyalkoxy)-1alpha,25-dihydroxyvi tam in D3: remarkably high affinity to vitamin D receptor.
[reaction: see text]A convenient and potentially valuable synthetic approach to the novel 2alpha-functionalized 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] derivatives (1a-c), which are the C2-epimer of ED-71 and its analogues, has been developed. The C2alpha-modified ring A precursors (1,7-enynes 16, n = 0, 1, and 2) were constructed stereoselectively starting from D-glucose in high yield. In the synthesized 2alpha-(omega-hydroxyalkoxy)-1alpha,25(OH)2D3 derivatives, 1a and 1b showed a greater binding affinity to vitamin D receptor (VDR), up to 1.8 times that of the native hormone.
Kittaka
A
A
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan.
Suhara
Y
Y
Takayanagi
H
H
Fujishima
T
T
Kurihara
M
M
Takayama
H
H
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D010165:Palladium; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013950:Thymus Gland / Q000378:metabolism
D018167:Receptors, Calcitriol; D010165:Palladium; D002117:Calcitriol