Synthesis and biological evaluation of 6-methyl analog of 1α,25-dihydroxyvitamin D3

Sokołowska, Katarzyna; Mouriño, Antonio; Siciński, Rafał R.; Sigüeiro, Rita; Plum, Lori A.; DeLuca, Hector F.

doi:10.1016/j.jsbmb.2010.02.008

Cited by 9 publications

(4 citation statements)

References 17 publications

(22 reference statements)

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“…Sheves and Mazur synthesized 6-methyl-vitamin D 3 ( 3 ) in 1976 and reported its tendency to undergo isomerization to the respective previtamin D form 7 ; a few years later, this analogue was also prepared by Yamada’s group . As an extension of these studies, we described the synthesis of 1α-hydroxy-6-methyl-vitamin D 3 ( 5 ) and 6-methyl-calcitriol ( 6 ) in 2005 and 2010, respectively . Similarly as in the case of 3 , these 6-methylated vitamins very easily equilibrated to their respective previtamin D forms 8 and 9 .…”

Section: Introductionmentioning

confidence: 92%

Synthesis and Biological Activity of Two C-7 Methyl Analogues of Vitamin D

et al. 2014

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Two novel vitamin D analogues of the hormone 1α,25-(OH)2D3 modified at C-7, namely, 7-methyl-1α,25-(OH)2D3 (12) and 7-methyl-1α,25-(OH)2-19-nor-D3 (26), were synthesized and biologically evaluated to gain further insights into the structure-function relationships of vitamin D. Key steps in the synthesis of 12 include the functionalization at C-7 by an efficient regioselective hydrostannylation of an allene precursor, and the construction of the triene framework by a palladium-catalyzed intramolecular cyclization-Suzuki-Miyaura coupling cascade. Since the calcitriol analogue 12 was prone to conversion into its previtamin D form by thermal equilibration, the corresponding 19-nor-compound 26 was also synthesized. The diene moiety of compound 26 was constructed by a modified Julia coupling. UV data as well as X-ray analysis indicate that introduction of the methyl group at C-7 results in a significant deviation from planarity of the 5,7-diene moiety. The new vitamin D analogues 12 and 26 retained good VDR binding ability.

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Section: Introductionmentioning

confidence: 92%

Synthesis and Biological Activity of Two C-7 Methyl Analogues of Vitamin D

et al. 2014

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“…Figure 19 (2009-2010) [271][272][273][274][275][276][277][278][279][280][281][282][283]. Intensive research activity was carried out on Gemini compounds 1053-1069 [273].…”

Section: Resultsmentioning

confidence: 99%

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

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Seoane

2022

Nutrients

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“…The relevance of this short pathway to 1,25D 3 analogs has been demonstrated by the intense synthetic activity used for the preparation of substituted A-ring-enyne synthons [68][69] and vitamin D analogs modified at the A-ring. [70][71][72][73][74][75][76][77][78][79][80] The relative high temperature (reflux in triethyl amine-toluene) required for the Pd(0)-catalyzed alkylative cyclization is unsuitable for the formation of vitamin D analogs that undergo thermal equilibration to the previtamin D form such as 6-methyl-25hydroxyvitamin D 3 , [43,81] and aromatic-D-ring analogs. [44,45]…”

Section: The Pd(0)-catalyzed Alkylative-cyclization Approach (G)mentioning

confidence: 99%

Pd(0)‐Catalyzed‐Mediated Synthesis of Vitamin D Compounds

Mouriño

2023

Adv Synth Catal

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Abstract1α,25‐Dihydroxyvitamin D3 (1,25D3), the hormonally active form of vitamin D3, regulates mineral homeostasis, cell growth, cell differentiation‐proliferation, apoptosis, and immune responses. 1,25D3 activates more than 229 genes associated with several diseases, including arthritis, diabetes and cancer, suggesting its implications in a broader range of biological functions than originally thought. Despite the wide range of biological activities, the clinical applications of 1,25D3 have been limited due to its collateral hypercalcemic effects. This problem has boosted intense synthetic activity in the vitamin D area in the last decades aimed at the development of highly active and non‐calcemic analogs for treatment of hyperproliferative diseases. This review covers the most useful synthetic approaches to 1,25D3 analogs containing the natural vitamin D triene system with emphasis on the Pd(0)‐catalyzed transformations involved in the formation of the vitamin D triene system and A‐ring synthons.

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Synthesis and biological evaluation of 6-methyl analog of 1α,25-dihydroxyvitamin D3

Cited by 9 publications

References 17 publications

Synthesis and Biological Activity of Two C-7 Methyl Analogues of Vitamin D

Synthesis and Biological Activity of Two C-7 Methyl Analogues of Vitamin D

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

Pd(0)‐Catalyzed‐Mediated Synthesis of Vitamin D Compounds

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