Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism-Reference-Cited by-同舟云学术

Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism

Published:2021-11-01 Issue:21 Volume:22 Page:11863
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

Kawagoe Fumihiro,Mototani Sayuri,Yasuda Kaori,Mano Hiroki,Sakaki Toshiyuki,Kittaka Atsushi^ORCID

Abstract

Two 24-fluoro-25-hydroxyvitamin D3 analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D3 side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D3 revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D3 (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.

Funder

Japan Society for the Promotion of Science

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Link

https://www.mdpi.com/1422-0067/22/21/11863/pdf

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