Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain |
| |
Authors: | Toshie Fujishima Takuro Komatsu Yuri Takao Wataru Yonamine Tsutomu Suenaga Hiroaki Isono Masayuki Morikawa Keisuke Takaguchi |
| |
Affiliation: | Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Shido, Sanuki, Kagawa, 769-2193, Japan |
| |
Abstract: | Five novel vitamin D analogues (2a, 2b, 3a, 3b and 4) bearing an aromatic side chain have been designed and synthesized in a convergent manner. The requisite CD-ring synthons (10a–c) were prepared from C22 aldehyde (5) using four- or five-step procedures. Using turbo-Grignard reagents allowed aromatic side chains with a polar functional moiety to be installed in a single step with excellent yields. A preliminary biological evaluation using bovine thymus vitamin D receptor (VDR) suggested that incorporating a carboxylic acid instead of the C25-hydroxy group had a positive effect on the VDR affinity compared with the corresponding esters. |
| |
Keywords: | Vitamin D Grignard reaction Vitamin D receptor Lactone Side-chain analogues |
本文献已被 ScienceDirect 等数据库收录! |