Synthesis of Vitamin D3and Calcitriol Dimers as Potential Chemical Inducers of Vitamin D Receptor Dimerization
- 1 November 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 65 (24) , 8290-8296
- https://doi.org/10.1021/jo001084x
Abstract
The design and synthesis of vitamin D3 dimers 2 and 3 and 1α,25-dihydroxyvitamin D3 (calcitriol) dimers 4 and 5 are described. The dimers were designed with a view to doubly binding the vitamin D receptor (VDR) and inducing the receptor homodimerization. In the dimers the units are linked through the C-11 position in ring C by an alkyl side chain of six or 10 carbon atoms, far from the hydroxy groups responsible for the VDR binding. The linker is formed by olefin metathesis of an olefinic side chain at the C-11 position introduced by stereoselective cuprate addition. The synthesis, which is both short and convergent, uses the Wittig−Horner approach to construct the vitamin D triene system and allows the preparation of dimers with a linker of modulated length with the purpose of optimizing the vitamin D3−VDR interaction.Keywords
This publication has 32 references indexed in Scilit:
- Mapping Phorbol Ester Binding Domains of Protein Kinase C (PKC): The Design, Synthesis and Biological Activity of Novel Phorbol Ester DimersSynthesis, 1999
- Rational Design, Synthesis, and Evaluation of a New Type of PKC InhibitorJournal of the American Chemical Society, 1998
- Tight Binding of a Dimeric Derivative of Vancomycin with Dimeric l-Lys-d-Ala-d-AlaJournal of the American Chemical Society, 1997
- Single-Step Synthesis of Cell-Permeable Protein Dimerizers That Activate Signal Transduction and Gene ExpressionJournal of the American Chemical Society, 1997
- Controlling programmed cell death with a cyclophilincyclosporin-based chemical inducer of dimerizationChemistry & Biology, 1996
- Dimeric ligands define a role for transcriptional activation domains in reinitiationNature, 1996
- Mechanistic studies of a signaling pathway activated by the organic dimerizer FK1012Chemistry & Biology, 1994
- Synthesis of (C-11)-substituted analogues of 1α,25-dihydroxyvitamin D3Bioorganic & Medicinal Chemistry Letters, 1992
- Studies on vitamin D (calciferol) and its analogs. 25. Studies on a convergent route to side-chain analogues of vitamin D: 25-hydroxy-23-oxavitamin D3The Journal of Organic Chemistry, 1983
- Tetrakis[iodo(tri‐n‐butylphosphine)copper(I)] and Iodo‐(2,2′‐Bipyridine)‐(Tri‐n‐butylphosphine)copper(I)Published by Wiley ,1963