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Design and concise synthesis of novel vitamin D analogues bearing a functionalized aromatic ring on the side chain

Author:
Fujishima, Toshie, Komatsu, Takuro, Takao, Yuri, Yonamine, Wataru, Suenaga, Tsutomu, Isono, Hiroaki, Morikawa, Masayuki, Takaguchi, Keisuke
Source:
Tetrahedron 2019 v.75 no.8 pp. 1098-1106
ISSN:
0040-4020
Subject:
aldehydes, aromatic compounds, calcitriol receptors, carboxylic acids, cattle, chemical reactions, esters, moieties, thymus gland, vitamin D
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.
Agid:
6289899