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

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.