Synthesis and biological activity of previtamin D3 analogues with A-ring modifications

Synthesis of two novel 6-s-cis analogues of 1α,25-dihydroxyvitamin D3 are described using shikimic acid and its 4-epi isomer as versatile chiral starting materials. These derivatives contain a 2β-(3′-hydroxypropoxy) moiety or a 2β,3β-epoxy group into 1α,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.

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