EurekaMag
+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Tabanidae
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Design, synthesis and biological properties of seco-d-ring modified 1α,25-dihydroxyvitamin D3 analogues


Design, synthesis and biological properties of seco-d-ring modified 1α,25-dihydroxyvitamin D3 analogues



Journal of Steroid Biochemistry and Molecular Biology 171: 144-154



ISSN/ISBN: 0960-0760

PMID: 28285018

DOI: 10.1016/j.jsbmb.2017.03.006

As a continuation of our efforts directed to the structure-activity relationship studies of vitamin D compounds, we present in this paper the synthesis of new analogues of 1α,25-(OH)2D3 characterized by numerous structural modifications, especially a cleaved D ring. Total synthesis of the CD fragment required for the construction of the target vitamins was based on the Stork approach. The structure of the key intermediate - bicyclic hydroxy lactone - was established by crystallographic and electronic circular dichroism (ECD) spectral analysis. Following the attachment of the hydroxyalkyl side chain, the formed D-seco Grundmann ketone was subjected to Wittig-Horner coupling with the corresponding A-ring phosphine oxides providing two desired D-seco analogues of 19-nor-1α,25-(OH)2D3, one without a substituent at C-2 and the other possessing a 2-exomethylene group. Both compounds were biologically tested and the latter was found to be more active in in vitro tests. Despite so many structural changes introduced in its structure, the biological activity of the 2-methylene analogue approached that of the natural hormone. The synthesized D-seco vitamins, however, proved to be inactive on bone and intestine in vivo.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 059589667

Download citation: RISBibTeXText

Related references

Novel furano analogues of duocarmycin C1 and C2: design, synthesis, and biological evaluation of seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues. Bioorganic and Medicinal Chemistry 10(9): 2941-2952, 2002

Synthesis and biological activity of 22-oxa CD-ring modified analogues of 1alpha,25-dihydroxyvitamin D3: spiro[5.5]undecane CF-ring analogues. Bioorganic and Medicinal Chemistry Letters 14(15): 3889-3892, 2004

Synthesis and biological activity of 22-oxa CD-ring modified analogues of 1alpha,25-dihydroxyvitamin D3: cis-perhydrindane CE-ring analogues. Bioorganic and Medicinal Chemistry Letters 14(15): 3885-3888, 2004

Biological activity of CD-ring modified 1alpha,25-dihydroxyvitamin D analogues: C-ring and five-membered D-ring analogues. Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research 15(2): 237-252, 2000

Design, synthesis, and biological studies of the A-ring-modified 1,25-dihydroxyvitamin D3 analogs. Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres Dans les Recherches sur le Cancer 164: 289-317, 2003

The synthesis of CD-ring modified 1-alpha,25-dihydroxyvitamin D analogues: Six-membered D-ring analogues I. Bioorganic and Medicinal Chemistry Letters 7(11): 1461-1464, 1997

The synthesis of CD-ring modified 1-alpha,25-dihydroxyvitamin D analogues: Six-membered D-ring analogues II. Bioorganic and Medicinal Chemistry Letters 7(11): 1465-1468, 1997

Synthesis of 1α,25-dihydroxyvitamin D3 analogues with α,α-difluorocycloketone at the CD-ring side chains and their biological properties in ovariectomized rats. Journal of Steroid Biochemistry and Molecular Biology 186: 66-73, 2019

Synthesis, biological activity, and conformational analysis of four seco-D-15,19-bisnor-1alpha,25-dihydroxyvitamin D analogues, diastereomeric at C17 and C20. Journal of Medicinal Chemistry 42(18): 3539-3556, 1999

Design, synthesis and biological evaluation of novel 1 alpha,25-dihydroxyvitamin D-3 analogues possessing aromatic ring on 2 alpha-position. Tetrahedron 61(47): 11253-11263, 2005

Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation. International Journal of Molecular Sciences 18(10), 2017

Synthetic strategy and biological activity of A-ring stereoisomers of 1,25- dihydroxyvitamin D3 and C2-modified analogues. Current Topics in Medicinal Chemistry 14(21): 2446-2453, 2014

Synthesis and biological evaluation of all A-ring stereoisomers of 5,6-trans-2-methyl-1,25-dihydroxyvitamin D(3) and their 20-epimers: possible binding modes of potent A-ring analogues to vitamin D receptor. Chemistry and Biology 8(11): 1011-1024, 2001

Methyl-introduced A-ring analogues of 1α,25-dihydroxyvitamin D3 : Synthesis and biological evaluation. International Symposium on Vitamin D Analogs in Cancer Prevention and Therapy 26(4A): 2633-2636, 2006

Design and synthesis of novel 1,25-dihydroxyvitamin D3 analogues having a spiro-oxetane fused at the C2 position in the A-ring. Bioorganic and Medicinal Chemistry 21(17): 5209-5217, 2013