Synthesis of two novel 6-s-cis analogues of 1 alpha,25-dihydroxyvitamin D-3 are described using shikimic acid and its 4-epi isomer as versatile chiral starting materials. These derivatives contain a 2b-(3'-hydroxypropoxy) moiety or a 2 beta,3 beta-epoxy group into 1 alpha,25-(OH)2-19-nor-pre-D-3. 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. (C) 2008 Elsevier Ltd. All rights reserved.