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Synthesis of a 1α-C-methyl analogue of 25-hydroxyvitamin D3: interaction with a mutant vitamin D receptor Arg274Leu
- Source :
- Tetrahedron. 65:7135-7145
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Vitamin D3 analogues have been developed for a mutant vitamin D receptor (VDR), Arg274Leu. The mutant VDR has a mutation at Arg274, which forms an important hydrogen bond with 1α-OH of 1α,25-dihydroxyvitamin D3 to anchor the ligand tightly in the VDR ligand binding pocket. Stereoselective synthesis of the A-ring part of the novel vitamin D analogue, 2α-(3-hydroxypropyl)-1α-methyl-25-hydroxyvitamin D3 (4), from d -galactose was accomplished with the key steps of the introduction of the methyl and allyl groups to the chiral building blocks. The new analogue 4 is ca. 7.3-fold more active than the natural hormone 1α,25-dihydroxyvitamin D3 (1).
- Subjects :
- Vitamin
Stereochemistry
medicine.medical_treatment
Organic Chemistry
Mutant
Ligand (biochemistry)
Biochemistry
Chemical synthesis
Calcitriol receptor
Steroid
chemistry.chemical_compound
chemistry
Drug Discovery
polycyclic compounds
Vitamin D and neurology
medicine
lipids (amino acids, peptides, and proteins)
Stereoselectivity
Subjects
Details
- ISSN :
- 00404020
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Tetrahedron
- Accession number :
- edsair.doi...........5828bb54b3e8fe3ada4ae7ab90689763