Design, Synthesis, Evaluation and Structure of Allenic 1α,25-Dihydroxyvitamin D₃ Analogs with Locked Mobility at C-17.

ABSTRACT: Vitamin D receptor ligands have potential for the treatment of hyperproliferative diseases and disorders related to the immune system. However, hypercalcemic effects limit their therapeutical uses and call for the development of tissue-selective new analogs. We have designed and synthesized the first examples of 1α,25-dihydroxyvitamin D₃ analogs bearing an allenic unit attached to the D ring to restrict the side-chain conformational mobility. The triene system was constructed by a Pd⁰ -mediated cyclization/Suzuki-Miyaura cross-coupling process in the presence of an allenic side chain. The allenic moiety was built through an orthoester-Claisen rearrangement of a propargylic alcohol. The biological activity and structure of (22S)-1α,25-dihydroxy-17,20-dien-24-homo-21-no

SUBMITTER: Fraga R 

PROVIDER: S-EPMC8519077 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature