57733-78-5Relevant articles and documents
Direct C(1) Hydroxylation of Vitamin D3 and Related Compounds
Paaren, Herbert E.,DeLuca, Hector F.,Schnoes, Heinrich K.
, p. 3253 - 3258 (1980)
A direct synthesis of C(1) hydroxylated vitamin D analogues from the corresponding vitamin D precursors has been developed.Allylic oxidation of 3,5-cyclovitamin D derivatives, readily obtained from the buffered solvolysis of vitamin D tosylates, with selenium dioxide yields 1α-hydroxylated 3,5-cyclovitamin D compounds which are smoothly converted to the desired 1α-hydroxyvitamin D derivatives by acid-catalyzed cycloreversion.Application of this scheme to vitamin D3 (1a), 25-hydroxyvitamin D3 (1b), and vitamin D2 (1c) affords the 1α-hydroxy products in ca.20 percent overall yield.
Method for preparing high-purity 1 alpha-hydroxyvitamin D3
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Paragraph 0025, (2018/03/01)
The invention discloses a method for preparing high-purity 1 alpha-hydroxyvitamin D3. The method comprises the following steps of (1) carrying out esterification; (2) carrying out cyclization; (3) carrying out oxidization; (4) carrying out ring opening; (5) carrying out photochemical isomerisation; (6) utilizing molecular sieve zeolite to carry out chiral purification and treatment on crude 1 alpha-hydroxyvitamin D3, and finally, carrying out recrystallization with an ethyl acetate-n-hexane system to obtain the high-purity 1 alpha-hydroxyvitamin D3. According to the method, by using a liposoluble solvent to replace pyridine and using an organic alkaline catalyst, under the condition with equivalent yield, the reaction temperature is changed from low temperature to room temperature, the reaction time is shortened, the pyridine with large pungent smell is avoided from using, and thus the economic practicability of the technology is greatly improved.
Synthesis and NMR studies of 13C-labeled vitamin D metabolites
Okamura, William H.,Zhu, Gui-Dong,Hill, David K.,Thomas, Richard J.,Ringe, Kerstin,Borchardt, Daniel B.,Norman, Anthony W.,Mueller, Leonard J.
, p. 1637 - 1650 (2007/10/03)
Isotope-labeled drug molecules may be useful for probing by NMR spectroscopy the conformation of ligand associated with biological hosts such as membranes and proteins. Triple-labeled [7,9,19-13C3]-vitamin D3 (56), its 25-hydroxylated and 1α,25-dihydroxylated metabolites (58 and 68, respectively), and other labeled materials have been synthesized via coupling of [9-13C]-Grundmann's ketone 39 or its protected 25-hydroxy derivative 43 with labeled A ring enyne fragments 25 or 26. The labeled CD-ring fragment 39 was prepared by a sequence involving Grignard addition of [13C]-methylmagnesium iodide to Grundmann's enone 28, oxidative cleavage, functional group modifications leading to seco-iodide 38, and finally a kinetic enolate SN2 cycloalkylation. The C-7,19 double labeling of the A-ring enyne was achieved by the Corey-Fuchs/Wittig processes on keto aldehyde 11. By employing these labeled fragments in the Wilson-Mazur route, the C-7,9,19 triple-13C-labeled metabolites 56, 58, and 68 as well as other 13C-labeled metabolites have been prepared. In an initial NMR investigation of one of the labeled metabolites prepared in this study, namely [7,9,19-13C3]-25-hydroxyvitamin D3 (58), the three 13C-labeled carbons of the otherwise water insoluble steroid could be clearly detected by 13C NMR analysis at 0.1 mM in a mixture of CD3OD/D2O (60/40) or in aqueous dimethylcyclodextrin solution and at 2 mM in 20 mM sodium dodecyl sulfate (SDS) aqueous micellar solution. In the SDS micellar solution, a double half-filter NOESY experiment revealed that the distance between the H19Z and H7 protons is significantly shorter than that of the corresponding distance calculated from the solid state (X-ray) structure of the free ligand. The NMR data in micelles reveals that 58 exists essentially completely in the α-conformer with the 3β-hydroxyl equatorially oriented, just as in the solid state. The shortened distance (H19Z-H7) in micellar solutions as compared to that in the solid state is most easily rationalized on the basis that the 5(10)-torsion angle in 58 is decreased in micellar solutions as compared to that in the solid state.
