214351-86-7Relevant articles and documents
Stereoselective Palladium-Catalyzed Approach to Vitamin D3 Derivatives in Protic Medium
Carballa, Diego,Sigüeiro, Rita,Rodríguez-Docampo, Zaida,Zacconi, Flavia,Maestro, Miguel A.,Mouri?o, Antonio
supporting information, p. 3314 - 3320 (2018/02/12)
We describe an efficient convergent synthesis of vitamin D3 metabolites and analogues. The synthetic strategy relies on a tandem Pd-catalyzed A-ring closure and Suzuki–Miyaura coupling to the CD-side chain component to set directly the vitamin D triene system under protic conditions. This strategy enables rapid access to vitamin D3 and 3-epi-vitamin D3 metabolites and analogues modified at the side chain for biological evaluation and structural and metabolic studies.
26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25- dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo
Grzywacz, Pawel,Plum, Lori A.,Clagett-Dame, Margaret,Deluca, Hector F.
, p. 9 - 16 (2013/05/09)
Twelve new analogs of 19-nor-1α,25-dihydroxyvitamin D3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, o
Synthesis of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]
Yoshino, Madoka,Eto, Kohei,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi,Ono, Yoshiyuki,Saito, Hitoshi,Kubodera, Noboru
experimental part, p. 381 - 394 (2010/09/05)
A convergent synthesis of biologically interesting 20-epi-eldecalcitol which possesses an inverted C-21 methyl substituent at the 20-position of the side chain of 1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3 (eldecalcitol) is described.
Synthesis and preliminary biological evaluation of 20-epi-eldecalcitol [20-epi-1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3: 20-epi-ED-71]
Hatakeyama, Susumi,Yoshino, Madoka,Eto, Kohei,Takahashi, Keisuke,Ishihara, Jun,Ono, Yoshiyuki,Saito, Hitoshi,Kubodera, Noboru
scheme or table, p. 25 - 28 (2011/12/01)
Eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3, developing code: ED-71] is an analog of active vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] that possesses a hydroxypropoxy substituent at the 2β-position of 1,25(OH)2D3. Eldecalcitol has potent biological effects on bone and is now in preparation for approval as a promising medicine for the treatment of osteoporosis in Japan. To explore chemical structure-biological activity relationships between eldecalcitol and related analogs, we have already synthesized 1-epi-eldecalcitol, 3-epi-eldecalcitol, and 1,3-diepi-eldecalcitol with inherent biological interests of each targeted analog and evaluated their biological responses. It has been reported that 20-epi-1,25(OH)2D3, a diastereomer of 1,25(OH)2D3 that possesses an inverted methyl substituent at the 20-position of the side chain, shows remarkably enhanced biological activities compared to parental compound, 1,25(OH)2D3. As a continuation of our modification studies on eldecalcitol, we took great interest in 20-epi-eldecalcitol and its biological responses. In this paper, the synthesis of 20-epi-eldecalcitol by the Trost coupling reaction between the A-ring fragment and the C/D-ring fragment as well as in vitro preliminary biological evaluation of 20-epi-eldecalcitol are described. In the induction of human myeloid leukemia cell (HL-60) differentiation, inhibition of the human histiocytic lymphoma cell (U937) proliferation, and increase in osteocalcin concentration in the human osteosarcoma cell (MG-63), 20-epi-eldecalcitol showed significantly enhanced activity compared to eldecalcitol.
2alpha-Methyl and 2beta-methyl analogs of 19,26,27-trinor-(20S)-1alpha-hydroxyvitamin D3 and their uses
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Page/Page column 4-5, (2010/11/08)
This invention discloses 2α-methyl and 2β-methyl analogs of 19,26,27-trinor-(20S) -1α-hydroxyvitamin D3 and pharmaceutical uses therefor. These compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells and i
2-METHYLENE-19,26,27-TRINOR-(20S)-1α-ALPHA-HYDROXYVITAMIN D3 AND ITS USES
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Page/Page column 11-12, (2010/11/08)
This invention discloses 2-methylene-19,26,27-trinor-(20S)-vitamin D analogs, and specifically 2-methylene-19,26,27-trinor-(20S)-lα-hydroxyvitamirt D3 and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the
19,26,27-TRINOR-1α,25-DIHYDROXYVITAMIN D3 COMPOUNDS
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Page/Page column 22-23, (2010/11/24)
Compounds of formula (1) are provided where X1, X2, and X3 are independently selected from H or hydroxy protecting groups, and R1 and R2 have the definitions provided herein. Such compounds may be used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.
Vitamin D analogs for obesity prevention and treatment
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, (2008/06/13)
Methods for treating and preventing obesity, inhibiting adipocyte differentiation, inhibiting increased SCD-1 gene transcription, and/or reducing body fat in a subject include administering at least one analog of 1α,25-dihydroxyvitamin D3 or 1α
Efficient synthesis and biological evaluation of all A-ring diastereomers of 1α,25-dihydroxyvitamin D3 and its 20-epimer
Fujishima, Toshie,Konno, Katsuhiro,Nakagawa, Kimie,Kurobe, Mayuko,Okano, Toshio,Takayama, Hiroaki
, p. 123 - 134 (2007/10/03)
An improved synthesis of the diastereomers of 1α,25-dihydroxyvitamin D3 (1) was accomplished utilizing our practical route to the A-ring synthon. We applied this procedure to synthesize for the first time all possible A- ring diastereomers of 20-epi-1α,25-dihydroxyvitamin D3 (2). Ten-step conversion of 1-(4-methoxyphenoxy)but-3-ene (6), including enantiomeric introduction of the C-3 hydroxyl group to the olefin by the Sharpless asymmetric dihydroxylation, provided all four possible stereoisomers of A- ring enynes (3), i.e., (3R,5R)-, (3R,5S)-, (3S,5R)- and (3S,5S)-bis[(tert- butyldimethylsilyl)oxy]oct-1-en-7-yne, in good overall yield. Palladium- catalyzed cross-coupling of the A-ring synthon with the 20-epi CD-ring portion (5), (E)-(20S)-de-A,B-8-(bromomethylene)cholestan-25-ol, followed by deprotection, afforded the requisite diastereomers of 20-epi-1α,25- dihydroxyvitamin D3 (2). The biological profiles of the synthesized stereoisomers were assessed in terms of affinities for vitamin D receptor (VDR) and vitamin D binding protein (DBP), HL-60 cell differentiation- inducing activity and in vivo calcium-regulating potency in comparison with the natural hormone. (C) 2000 Elsevier Science Ltd.
Synthesis and biological activity of 2-methyl-20-epi analogues of 1α,25-dihydroxyvitamin D3
Fujishima, Toshie,Liu, Zhaopeng,Miura, Daishiro,Chokki, Manabu,Ishizuka, Seiichi,Konno, Katsuhiro,Takayama, Hiroaki
, p. 2145 - 2148 (2007/10/03)
Synthesis and biological evaluation of all eight possible A-ring diastereomers of 2-methyl-20-epi-1,25-dihydroxyvitamin D3 are described. Among the analogues synthesized, 2α-methyl-20-epi-1α,25-dihydroxyvitamin D3 exhibited exceptionally high potency. The double modification of 2- methyl substitution and 20-epimerization yielded analogues with unique activity profiles.