- Preparation method of 25-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3 and isotope internal standard compound thereof
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The invention discloses a preparation method of 25-hydroxyvitamin D3 and 1alpha, 25-dihydroxyvitamin D3 and an isotope internal standard compound thereof. The preparation method comprises the following steps: a compound III is subjected to SO2 conjugate protection, O3 oxidation, NaBH4 reduction, iodination ring opening, conjugate addition with acrylate, and reaction with a methyl Grignard reagentor isotope labeled methyl Grignard reagent, a silicon protecting group is removed under the action of TBAF, and a product is obtained through ultraviolet irradiation configuration inversion under thecatalysis of 9-acetyl anthracene. The method is good in reaction selectivity, high in total yield, simple and convenient to operate and short in isotope introduction step, and the isotope utilizationrate is greatly increased.
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- Revisiting the 7,8-cis-Vitamin D3 derivatives: Synthesis, evaluating the biological activity, and study of the binding configuration
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Four 7,8-cis-1α,25-dihydroxyVitamin D3 derivatives, 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxy-19-norVitamin D3 as well as 7,8-cis- and 7,8-cis-14-epi-1α,25-dihydroxyVitamin D3 were synthesized, and their chemical stabili
- Sawada, Daisuke,Kakuda, Shinji,Kamimura-Takimoto, Midori,Takeuchi, Akiko,Matsumoto, Yotaro,Kittaka, Atsushi
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p. 2838 - 2848
(2016/05/19)
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- Nickel-Mediated Conjugate Addition. Elaboration of Calcitriol from Ergocalciferol
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A convenient method for introduction the side chain of the hormone calcitriol (3) was achieved by coupling the nickel(0) complex derived from ethyl acrylate with the C-22 iodides 15, 16, 27, and 30 to give the corresponding esters 18, 21, 28, and 23 in yields of 73-82percent.Iodide 15 was also coupled with the Ni(0) complex derived from methyl vinyl ketone.The C-22 iodides 15 and 27 were obtained from ergocalciferol (6) and the 1(S),3(R)-bis-(5E,7E)-ergocalciferol derivative 24, respectively, by selective ozonolysis of their SO2 adducts, followed by in situ reduction of the ozonides with NaBH4 and iodination of the derived alcohols 14 and 26 with I2/PPh3/imidazole.The triene iodide 16 was prepared by extrusion of SO2 from 15, while 30 was obtained from the corresponding alcohol 29.Extrusion of SO2 from 21 and 28 gave the 5(E),7(E)-trienes 18 and 23, respectively.The latter was also made from the former by C-1 hydroxylation with selenium dioxide followed by silylation with tert-butyldimethylsilyl chloride and chromatographic separation.Completion of the synthesis of 3 was accomplished by treating 23 with methylmagnesium bromide to give 31, followed by desilylation with n-Bu4NF and triplet-sensitized photoisomerization.Alternatively, 31 was photoisomerized to 33, desilylation of which gave 3.Alcohol 33 was also prepared by the reaction of the 5Z,7E-triene ester 34, which was obtained by the photoisomerization of 23, with methylmagnesium bromide.
- Manchand, Percy S.,Yinnikouros, George P.,Belica, Peter S.,Madan, Pradeep
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p. 6574 - 6581
(2007/10/03)
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- 7,8-Cis geometric isomers of the steroid hormone 1α,25-dihydroxyvitamin D3
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The syntheses of the previously unknown, sterically hindered geometric isomers 3 and 4 of the steroid hormone 1α,25-dihydroxyvitamin D3(1,1,25) have been achieved for the first time. The stereoselective synthesis of the vinylallene precursor 23a was achieved by the Inanaga method, Pd(0)-Sm(II)-iPrOH reduction of propargyl benzoate 33. The latter observation reveals that the Inanaga propargyl ester to allene transformation is in fact stereoselective (～10:1), involving a formal anti-SN2′ displacement of benzoate by hydrogen. Highly stereoselective (50:1, 85% yield) (1,5)-hydrogen shift of vinylallene 23a to the sterically hindered 7,8-cis isomer of the hormone 1, namely, 3, was achieved by the Shibasaki method using (naphthalene)tricarbonylchromium (22, (np)(CO)3Cr). By examining this chromium-(0)-mediated isomerization on all four diastereomeric vinylallene analogue systems 6a,b and 7a,b, all of which resulted highly selectively (50:1) in hindered 7,8-cis geometric isomers, new stereomechanistic information concerning the Shibasaki type 1,5-shift has also emerged. By cheleotropic addition-extrusion of sulfur dioxide on 3, there was obtained the final unknown geometric isomer of 1, 5,6-trans-7,8-cis-1,25 4; this result parallels the known transformation of 1 to 2. Although the vinylallene 23a can be thermally rearranged via a [1,5]-sigmatropic hydrogen shift to the natural hormone 1, the yield and selectivity are modest. By contrast, one-way triplet photosensitized isomerism of the now readily available 7,8-cis-isomer 3 results primarily in the natural hormone 1 in good yield and selectivity. Taken collectively, these observations reveal that the synthesis of all four geometric isomers 1-4 can be achieved from a single precursor, the vinylallene 23a. Comparative biochemical evaluation, in vitro, of the four geometric isomers in terms of their ability to bind to the chick intestinal receptor reveals that 7,8-cis isomerism (3 and 4) significantly suppresses their ability to bind receptor (2% each versus 100% for the hormone 1,25).
- VanAlstyne, Ellen M.,Norman, Anthony W.,Okamura, William H.
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p. 6207 - 6216
(2007/10/02)
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- Direct C(1) Hydroxylation of Vitamin D3 and Related Compounds
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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.
- Paaren, Herbert E.,DeLuca, Hector F.,Schnoes, Heinrich K.
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p. 3253 - 3258
(2007/10/02)
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