Revisiting the 7,8-cis-vitamin D sub(3) derivatives: synthesis, evaluating the biological activity, and study of the binding configuration
Four 7,8-cis-1 alpha ,25-dihydroxyvitamin D sub(3) derivatives, 7,8-cis- and 7,8-cis-14-epi-1 alpha ,25-dihydroxy-19-norvitamin D sub(3) as well as 7,8-cis- and 7,8-cis-14-epi-1 alpha ,25-dihydroxyvitamin D sub(3) were synthesized, and their chemical stability was characterized. In our previous work...
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| Published in: | Tetrahedron Vol. 72; no. 22; pp. 2838 - 2848 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
02-06-2016
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Four 7,8-cis-1 alpha ,25-dihydroxyvitamin D sub(3) derivatives, 7,8-cis- and 7,8-cis-14-epi-1 alpha ,25-dihydroxy-19-norvitamin D sub(3) as well as 7,8-cis- and 7,8-cis-14-epi-1 alpha ,25-dihydroxyvitamin D sub(3) were synthesized, and their chemical stability was characterized. In our previous work, we disclosed that 14-epi-19-nortachysterol showed the unprecedented binding configuration in human vitamin D receptor (hVDR), that is, 5,6- and 7,8-s-trans configuration. However, this configuration is variable because of the rotation at the single bond between C7 and C8. For the precise discussion of the 7,8-s-trans configuration, we designed and synthesized the 7,8-cis-locked skeleton of vitamin D sub(3) derivatives. Among four analogs, the 19-nor derivatives were stable at ambient temperature, and their hVDR binding affinity and co-crystallographic analysis of their hVDR complexes were studied. The other derivatives with the triene system were isomerized to corresponding previtamin D sub(3) and vitamin D sub(3). |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
| ISSN: | 0040-4020 |
| DOI: | 10.1016/j.tet.2016.03.081 |