116535-65-0

Usage

Chemical Properties

Light Yellow Solid

Uses

Intermediate in the preparation of Calcifediol.

Upstream product

• 66774-80-9 (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 
• 64190-52-9 (8S,20S)-de-A,B-20-(hydroxymethyl)pregnan-8-ol 

Downstream Products

• 1356484-64-4 ethyl 2-{(S)-2-[(1R,3aS,7aR,E)-4-((Z)-2-{(3S,5R)-3,5-bis[(tert-butyldimethylsilyl)oxy]-2-methylenecyclohexylidene}ethylidene)-7a-methyloctahydro-1H-inden-1-yl]propyl}-2H-tetrazole-5-carboxylate 
• 131918-61-1 paricalcitol 
• 1263286-73-2 (7E)-(1R,3R)-24-phenylsulfonyl-9,10-seco-19,22,23-trinorchola-5,7-dien-1,3-diol 
• 1263286-72-1 (7E)-(1R,3R)-24-phenylsulfonyl-1,3-bis(tert-butyldimethylsililoxy)-9,10-seco-19,22,23-trinorchola-5,7-dien 
• 1263286-71-0 (7aR)-7a-methyl-1-((S)-1'-(phenylsulfonyl)propane-2'-yl)hexahydro-1H-inden-4(2H)-on 
• 132015-95-3 (1R,3R,7E,22E,24R)-24-methyl-19-nor-9,10-secocholesta-5,7,22-triene-1,3,25-triol 
• 1263286-75-4 (1R,3R,7E,22E,24E)-24a-homo-19-nor-9,10-secoergosta-5,7,22,24-tetraen-1,3,25-triol 
• 1263286-76-5 (1R,3R,7E,22E,24E)-24a-homo-19-nor-9,10-secoergosta-5,7,22,24-tetraen-1,3,25-triol 
• 93489-60-2 <1R-<1β(R*),3aα,4β,7aβ>>-octahydro-4-hydroxy-β,7a-dimethyl-1H-indene-1-propanenitrile 
• 70550-73-1 (1R,3aR,7aR)-1-[(2R)-6-hydroxy-6-methylhept-2-yl]-7a-methyloctahydroinden-4-one 
• 66774-84-3 de-A,B-25-hydroxycholestan-8β-ol 
• 1428964-47-9 (20R)-1α-[(tert-butyldimethylsilyl)oxy]-2-methylene-19,26,27-trinorvitamin D₃ tert-butyldimethylsilyl ether 

Relevant academic research and scientific papers

Introduction of fluorine atoms to vitamin D3 side-chain and synthesis of 24,24-difluoro-25-hydroxyvitamin D3 　

During our ongoing studies of vitamin D, we focused on the vitamin D3 side-chain 24-position, which is the major metabolic site of human CYP24A1. In order to inhibit the metabolism of vitamin D3, 24,24-difluorovitamin D3analogues are important candidates. In this paper, we report the practical introduction of the difluoro-unit to the 24-position to synthesize 24,24-difluoro-CD ring (1) and 24,24-difluoro-25-hydroxyvitamin D3 (2).

Preparation method of activated vitamin D3 drug CD ring intermediate

The invention relates to a preparation method of an activated vitamin D3 drug CD ring intermediate. The preparation method comprises the following steps: carrying out iodine substitution on a diol derivative 2 to obtain a compound 3, carrying out hydroxyl reaction on the compound 3 to obtain a compound 4, carrying out Michael addition reaction on the compound 4 to obtain a compound 5, carrying out nucleophilic addition reaction on the compound 5 to obtain a compound 6, carrying out deprotection reaction on the compound 6 to obtain a compound 7, and carrying out oxidation reaction on the compound 7 to obtain a compound 1, namely, the activated vitamin D3 drug CD ring intermediate (25-hydroxy Grundmann's one). The preparation method provided by the invention has the advantages that the steps are simple, the product yield is high, and massive 25-hydroxy Grundmann's one can be prepared.

VITAMIN D3 DERIVATIVES AND PHARMACEUTICAL USE THEREOF

The present invention relates to vitamin D3 derivatives of the following formula, wherein each symbol has the same meaning as defined herein, and pharmaceutical or medical use thereof for treating metabolic disease, liver disease, obesity, diabetes, cardiovascular disease, or cancer in a patient in need thereof.

NEW SYNTHONES FOR PREPARATION OF 19-NOR VITAMIN D DERIVATIVES

The present invention discloses the synthone of Formula (I), wherein R1 and R2 are the same or different and represent independently hydrogen atom or hydroxyl protecting group, and its use for preparation of 19-nor vitamin D derivatives of general Formula (IV), wherein represents single or double bond, p represents an integer 0 to 3, R1 and R2 represent independently hydrogen atom or hydroxyl protecting group, R3 represents hydrogen atom, CH3 or hydroxyl group, R4, R5 and R6 represent independently hydrogen atom, C1-C3-alkyl or hydroxyl group or two of R4, R5 and R6 substituents altogether form cyclopropyl group, in particular for preparation of paricalcitol.

26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25- dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

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

Vitamin D heterocyclic analogues; Part 2: Synthesis of the first vitamin D analogues with a tetrazole ring at the side chain

Access to the calcitriol analogues with a tetrazole ring at the side chain was very efficiently achieved using the Calverley-Choudhry approach instead of the Wittig-Horner method, which gave very low yields. Georg Thieme Verlag Stuttgart. New York.

Synthesis and biological activities of the two C(23) epimers of 1α,23,25-trihydroxy-24-oxo-19-nor-vitamin D3: Novel analogs of 1α,23(S),25-trihydroxy-24-oxo-vitamin D3, a natural metabolite of 1α,25- dihydroxyvitamin D3

In a previous report, we indicated that 1α,23(S),25-trihydroxy-24- oxovitamin D3 [1α,23(S),25(OH)3-24-oxo-D3], a natural metabolite of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is almost equipotent to 1α,25(OH)2D3 in suppressing parathyroid hormone (PTH) secretion (Lee et al., 1997. Biochemistry 36, 9429-9437). Also, 1α,23(S),25(OH)3-24-oxo-D3 has been shown to possess only weak in vivo calcemic actions. Thus, vitamin D3 analogs structurally related to 1α,23(S),25(OH)3-24-oxo-D3 may have therapeutic value. Furthermore, biologic activity studies of various synthetic analogs of 1α,25(OH)2D3 showed that the removal of carbon-19 (C- 19) reduces the calcemic activity of 1α,25(OH)2D3. Therefore, in an attempt to produce vitamin D3 analogs with a better therapeutic index, we synthesized C(23) epimers of 1α,23,25(OH)3-24-oxo-19-nor-vitamin D3 [1α,23,25(OH)3-24-oxo-19-nor-D3]. The two epimers were compared to 1α,25(OH)2-19-nor-D3 and 1α,25(OH)2D3 in their ability to generate biologic activities in several in vitro assay systems. In the assay measuring the suppression of parathyroid hormone (PTH) secretion in bovine parathyroid cells, 1α,23(S),25(OH)3-24-oxo-19-nor-D3 was as potent as 1α,25(OH)2-19- nor-D3 but was less potent than 1α,25(OH)2D3. In the same assay 1α,23(R),25(OH)3-24-oxo-19-nor-D3 exhibited greater potency than 1α,23(S),25(OH)3-24-oxo-19-nor-D3. In the assays measuring the ability of vitamin D compounds to inhibit clonal growth and to induce differentiation of human promyelocytic leukemia (HL-60) cells, 1α,23(S),25(OH)3-24-oxo-19-nor- D3 was less potent than 1α,25(OH)2-19-nor-D3 but was equipotent to 1α,25(OH)2D3. More importantly, in the same assays, 1α,23(R),25(OH)3-24- oxo-19-nor-D3 was more potent than 1α,23(S),25(OH)3-24-oxo-19-nor-D3 and was equipotent to 1α,25(OH)2-19-nor-D3. Also, the vitamin D receptor- mediated transcriptional activity of 1α,23(R),25(OH)3-24-oxo-19-nor-D3 was almost equal to that of 1α,25(OH)2-19-nor-D3, but higher than that of 1α,23(S),25(OH)3-24-oxo-19-nor-D3. This finding explains in part the greater in vitro biologic activities of 1α,23(R),25(OH)3-24-oxo-19-nor-D3. In summary, our results indicate that 1α,23(R),25(OH)3-24-oxo-19-nor-D3 and to a lesser extent 1α,23(S),25(OH)3-24-oxo-19-nor-D3 are potent 19-nor vitamin D3 analogs, which suppress PTH secretion in bovine parathyroid cells and strongly inhibit clonal growth and induce differentiation of HL-60 cells in vitro. (C) 2000 Elsevier Science Inc.

Ultrasonically Induced Conjugate Addition of Iodides to Electron-Deficient Olefins and Its Application to the Synthesis of Side-Chain Analogs of the Hormone 1α,25-Dihydroxyvitamin D3

A versatile method for the rapid construction of fragments related to the upper part of vitamin D3 from the Lythgoe-Inhoffen diol is described.The key feature of the strategy is a new zinc-copper-induced conjugate addition of iodo triflate 10a to electron-deficient olefins under sonochemical aqueous conditions.These fragments are rapidly and efficiently transformed via the dienyne convergent approach to several derivatives of the hormone 1α,25-(OH)2-D3 modified at C-25.

New one-pot synthesis of alkyl nitrates from alcohols

Treatment of alcohols with Ph3P-I2-imidazole followed by 'in situ' reaction of the generated iodides with AgNO3 allows the mild conversion of alcohols into alkyl nitrates. Unlike previous procedures, this one requires no electrophilic nitrating conditions.

Palladium-catalysed coupling of vinyl triflates with enynes and its application to the synthesis of 1α,25-dihydroxyvitamin D3

We describe a general approach, based on the palladium-catalysed coupling of enynes with vinyl triflates, for the construction of dienynes related to vitamin D metabolites and analogues. As an application of this method, an efficient convergent synthesis of 1α,25-dihydroxyvitamin D3 starting from the Inhoffen-Lythgoe diol (6a) and natural carvones has been carried out (11 steps, 28% overall yield from 6a). This strategy allows labelling of the side chain in the final steps of the synthesis.