RT Journal Article
T1 Design, synthesis, evaluation and structure of Allenic 1α,25-Dihydroxyvitamin D3 analogs with locked mobility at C-17
A1 Fraga Mallo, Ramón
A1 Len, Kateryna
A1 Regis, Lutzing
A1 Laverny, Gilles
A1 Loureiro, Julián
A1 Maestro Saavedra, Miguel Anxo
A1 Rochel, Natacha
A1 Rodriguez-Borges, José Enrique
A1 Mouriño Mosquera, Antonio
K1 Allenes
K1 Orthoester-Claisen rearrangement
K1 Pdcatalyzed reactions
K1 Synthesis
K1 Vitamin D analogs
AB 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-nor-vitamin D3 bound to binding domain of the vitamin D receptor, provide information concerning side-chain conformational requirements for biological activity
PB Wiley
YR 2021
FD 2021
LK http://hdl.handle.net/10347/29060
UL http://hdl.handle.net/10347/29060
LA eng
NO Chem. Eur. J. 2021, 27, 13384–1338. https://doi.org/10.1002/chem.202101578
NO We thank FCT of Portugal (project PTDC/BIA-MIB/29059/2017), UIDB/50006/2020 to LAQV-REQUIMTE Research Unit, the European Union (European Regional Development Fund-ERDF), and Xunta de Galicia, Spain (GRC/ED431B/2018/13), for financial support. We also thank the Ligue contre le cancer, Agence Nationale de la Recherche ANR-13-BSV8-0024-01, and institucional funds from Instruct-ERIC for support and use of resources of the French Infrastructure for Integrated Structural Biology (ANR-10-LABX-0030-INRT and ANR-10-IDEX-0002-02). ERB and JL thank FCT (SFRH/BSAB/150309/2019) and (PTDC/BIA-MIB/29059, 2017-REQUIMTE2019-86) for postdoctoral fellowships, respectively
DS Minerva
RD 9 jun 2026