Design, Synthesis, Evaluation and Structure of Allenic 1 alpha,25-Dihydroxyvitamin D-3 Analogs with Locked Mobility at C-17

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Fraga, R (Author) Other; Len, K (Author) Other; Lutzing, R (Author) Other; Laverny, G (Author) Other; Loureiro, J (Author) Other; Maestro, MA (Author) Other; Rochel, N (Author) Other; Rodriguez Borges, JE (Author) FCUP; Mourio, A (Author) Other

Journal

Title: Chemistry - A European Journal

Vol. 27

ISSN: 0947-6539

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 3 Citations

Other information

Authenticus ID: P-00V-8X3

DOI: 10.1002/chem.202101578

Abstract (EN): 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 1 alpha,25-dihydroxyvitamin D-3 analogs bearing an allenic unit attached to the D ring to restrict the side-chain conformational mobility. The triene system was constructed by a Pd-0-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)-1 alpha,25-dihydroxy-17,20-dien-24-homo-21-nor-vitamin D-3 bound to binding domain of the vitamin D receptor, provide information concerning side-chain conformational requirements for biological activity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6