Chemical conversion of vitamin D3 to its 1,35-dihydroxy metabolite

Kiegiel, Katarzyna; Wovkulich, Peter M.; Uskoković, Milan R.

doi:10.1016/0040-4039(91)80752-r

Cited by 51 publications

(23 citation statements)

References 18 publications

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“…The synthesis (Scheme 6) started again from Grundmann ketone 4, 18 which was selectively hydroxylated at C-25 by ruthenium-catalyzed oxidation 28,29 to give 21. After TES ether protection of the C-25 hydroxy group, the resulting ketone 22 30 was converted to corresponding enone 23.…”

Section: Resultsmentioning

confidence: 99%

“…After stirred for 2 h at À78 C, the reaction was quenched by addition of methanol (0.5 mL), and was then diluted with diethyl ether (20 mL), washed with, successively, saturated aq NH 4 Cl, water and brine, and dried (MgSO 4 ), and evaporated. The residue was purified by column chromatography (28). TESCl (0.05 mL, 0.30 mmol) was added to a stirred solution of 19 (67 mg, 0.20 mmol) and imidazole (41 mg, 0.60 mmol) in dry DMF (1 mL).…”

Section: General Materials and Methodsmentioning

confidence: 99%

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Synthesis of C-11 linked active ester derivatives of vitamin D3 and their conjugations to 42-residue helix–loop–helix peptides

et al. 2010

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Section: Resultsmentioning

confidence: 99%

Section: General Materials and Methodsmentioning

confidence: 99%

Synthesis of C-11 linked active ester derivatives of vitamin D3 and their conjugations to 42-residue helix–loop–helix peptides

et al. 2010

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“…Grundmann's ketone is a product of ozonolysis of vitamin D 3 ; its selective 25‐hydroxylation is part of a synthetic route to vitamin D 3 metabolites and derivatives. Chemical synthesis of 25‐hydroxy Grundmann's ketone by using ruthenium catalysts has been reported 26. The workup of the ruthenium‐catalyzed reaction is laborious, and the remaining Grundmann's ketone ( 33 ) has to be recovered by column chromatography; the overall yield was reported as 49 % 26.…”

Section: Discussionmentioning

confidence: 99%

Cluster Screening: An Effective Approach for Probing the Substrate Space of Uncharacterized Cytochrome P450s

2013

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Cytochrome P450 monooxygenases (P450s) are versatile enzymes with high potential for biocatalysis. The number of newly annotated P450 genes has been increasing constantly, and these thus represent a rich resource for new biocatalysts. However, the substrate scopes of newly identified P450s are often not known, and thus their exploitation is difficult. Herein we describe an approach, named "cluster screening", and its application for the primary characterization of two P450s: CYP154E1 and CYP154A8. A library comprising 51 compounds was designed and organized into nine groups according to their chemical properties. The activities of both P450s in vitro were maintained with suitable nonphysiological redox partners, and the cluster library was screened with these enzymes for product formation. From this library, 30 compounds tested positive for CYP154E1 and 23 were positive for CYP154A8. Cluster screening distinguishes subtle differences in activity and selectivity of enzymes as closely related as those of the same P450 family. For example, the alkaloid pergolide mesylate was converted by CYP154E1 (4 %) but not by CYP154A8. A building block of vitamin D3 , Grundmann's ketone, was converted by both enzymes, although conversion was higher with CYP154E1 (100 vs 53%).

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“…The reaction of the corresponding t-butyl ester of 29 with DAST in trichloroethylene at -78 °C gave the corresponding 1 -fluorinated compound in 70% yield [33]. An alternative approach to introduce fluorine with DAST was accomplished in excellent yield using a substrate derived from vitamin D 3 with epoxide protection [35].…”

Section: Vitamin D Analogues Having Fluorine Instead Of Hydroxyl Groupsmentioning

confidence: 99%

Synthesis and Biological Activity of Fluorinated Vitamin D

Fujishima¹,

Fujii²,

Harayama

2010

COC

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The active metabolite of vitamin D, 1 ,25-dihydroxyvitamin D3 (1), has a wide range of biological activities, making its analogues promising therapeutic agents for the treatment of cancer, psoriasis and osteoporosis. In particular, the stability of the carbonfluorine bond to oxidation has aided in the development of fluorinated vitamin D analogues as catabolism inhibitors. The analogues were synthesized either by classical steroidal approaches or by convergent methods, depending on the sites of fluorination. The incorporation of fluorine has provided numerous advantages for studying the structurally flexible hormone 1 ,25-dihydroxyvitamin D3 1, including helping to define its molecular mode of actions. Biological evaluation of the fluorinated analogues suggested that fluorine substitution would not only change the metabolism, but also have direct effects on the vitamin D receptor, resulting in compounds with unique activity profiles.

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Chemical conversion of vitamin D3 to its 1,35-dihydroxy metabolite

Cited by 51 publications

References 18 publications

Synthesis of C-11 linked active ester derivatives of vitamin D3 and their conjugations to 42-residue helix–loop–helix peptides

Synthesis of C-11 linked active ester derivatives of vitamin D3 and their conjugations to 42-residue helix–loop–helix peptides

Cluster Screening: An Effective Approach for Probing the Substrate Space of Uncharacterized Cytochrome P450s

Synthesis and Biological Activity of Fluorinated Vitamin D

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