Ring c aromatic steroids. Part 2. Rearrangement of 16α,17α-epoxy-and 17α-hydroxy-5,7-dienes

Bridgewater, A.J.; Cheung, H. T. Andrew; Vadasz, Andrew; Watson, T. R.

doi:10.1039/p19800000556

Cited by 10 publications

(11 citation statements)

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“…Here we report on the UVB photolysis of 3β,21-dihydroxypregna-5,7-dien-20-one [33] synthesized from 3-acetylated 5-diene precursor [34, 35]. The photolytic reaction led to synthesis of novel 9,10-secosteroids with vitamin D and lumisterol backbone structures, and oxidized derivatives.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and photochemical transformation of 3β,21-dihydroxypregna-5,7-dien-20-one to novel secosteroids that show anti-melanoma activity

Żmijewski

Chen

et al. 2011

Steroids

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We have synthesized 3β,21-dihydroxypregna-5,7-dien-20-one (21(OH) 7DHP) and used UVB radiation to induce its photoconversion to analogues of vitamin D (pD), lumisterol (pL) and tachysterol (pT). The number and character of the products and the dynamics of the process were dependent on the UVB dose. The main products: pD and pT compounds were characterized by UV absorption, MS and NMR spectroscopy after RP-HPLC chromatography. In addition, formation of multiple oxidized derivatives of the primary products was detected and one of these derivatives was characterized as oxidized 21-hydroxyisotachysterol compound (21(OH)oxy-piT). These newly synthesized compounds inhibited growth of human melanoma cells in a dose dependent manner, with greater or equal potency to calcitriol. 3β,21-Dihydroxy-9β,10α-pregna-5,7-dien-20-one (21(OH)pL) and 21(OH)oxy-piT had higher potency against pigmented melanoma cells, while the EC 50 for compounds 21(OH)7DHP and (5Z,7E)-3β,21-dihydroxy-9,10-secopregna-5,7,10(19)-trien-20-one (21(OH)pD) were similar in both pigmented and nonpigmented cells. Moreover, 21(OH)7DHP and its derivatives inhibited proliferation of human epidermal HaCaT keratinocytes, albeit at a lower activity compared to melanoma cells. Importantly, 21(OH)7DHP derivatives strongly inhibited the colony formation of human melanoma cells with 21(OH)pD being the most potent. The potential mechanism of action of newly synthesized compounds was similar to that mediated by 1,25(OH) 2 D 3 and involved ligandinduced translocation of vitamin D receptor into the nucleus. In summary, we have characterized for the first time products of UVB-induced conversion of 21(OH)7DHP and documented that these compounds have selective, inhibitory effects on melanoma cells.

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Section: Introductionmentioning

confidence: 99%

Synthesis and photochemical transformation of 3β,21-dihydroxypregna-5,7-dien-20-one to novel secosteroids that show anti-melanoma activity

Żmijewski

Chen

et al. 2011

Steroids

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“…[13,19] The dynamics of the photolytic reactions and identification of novel 9,10-secosteroids with D- T- and L-like structures, and corresponding 5,7,9(11)-trienes. In addition, we studied the formation of secosteroidal derivatives in human skin exposed to UVB and tested their biological activity on the human melanoma SKMEL-188 cell line.…”

Section: Introductionmentioning

confidence: 99%

Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3β, 17α, 20-triol and their bioactivity in melanoma cells

Żmijewski

Zjawiony

et al. 2009

Steroids

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Pregna-5,7-dienes and their hydroxylated derivatives can be formed in vivo when there is a deficiency in 7-dehydrocholesterol (7-DHC) Δ-reductase function, e.g., Smith-Lemli-Opitz syndrome (SLOS). Ultraviolet B (UVB) radiation induces photoconversion of 7-DHC to vitamin D 3 , lumisterol 3 and tachysterol 3 . Two epimers (20R and 20S) of pregna-5,7-diene-3β,17α,20-triol (4R and 4S, respectively) were synthesized and their UVB photo-conversion products identified as corresponding 9,10-secosteroids with vitamin D-like and tachysterol-like structures, and 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol-like). The number and character of the products and the dynamics of the process were dependent on the UVB dose. At high UVB doses, the formation of multiple oxidized derivatives of the primary products, and the formation of 5,7,9(11)-triene, were observed. The production of vitamin D-like, tachysterol-like and luminosterol-like derivatives was also observed in human skin treated with 4R and 4S, and subjected to UV irradiation, as shown by RP-HPLC. Newly synthesized compounds inhibited melanoma growth in dose dependent manner, and some of them showed equal or higher potency than 1,25(OH) 2 D 3 . In summary, we have characterized for the first time the products of UV induced conversion of pregna-5,7-diene-3β,17α, 20-triols and documented that the newly synthesized compounds have antiproliferative properties against melanoma cells.

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“…To overcome this situation, the reaction has been generally performed in Ac 2 O as solvent. 23,24 Under these reaction conditions, it has been assumed that the rearrangement firstly affords the 16a-hydroxy rearranged products, which after fast acylation gives 16a-acetoxy-17b-methyl-D 13 -18-norsteroids, in good to high yields. These compounds do not undergo further isomerization at C16, and therefore more selective transformations were achieved.…”

Section: Introductionmentioning

confidence: 99%

“…Although several authors described the use of Ac 2 O as solvent to perform this rearrangement, 23,24 we started our study using 1.5 equiv of Ac 2 O in MeNO 2 , at 50 C, in the presence of 5 mol % of Bi(OTf) 3 $xH 2 O. However, as observed by TLC control, the C16-epimerization still occurred and both rearranged products 2 and 3 were detected, along with minor side products, after 24 h of reaction.…”

Section: Introductionmentioning

confidence: 99%

Bismuth(III) triflate-catalyzed rearrangement of 16α,17α-epoxy-20-oxosteroids. Synthesis and structural elucidation of new 16α-substituted 17α-alkyl-17β-methyl-Δ13-18-norsteroids

et al. 2009

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Ring c aromatic steroids. Part 2. Rearrangement of 16α,17α-epoxy-and 17α-hydroxy-5,7-dienes

Abstract: Ring c Aromatic Steroids. Part 2.l Rearrangement of 16ar,l7a-Epoxyand 17a-Hydroxy-5,7-dienes

Cited by 10 publications

References 0 publications

Synthesis and photochemical transformation of 3β,21-dihydroxypregna-5,7-dien-20-one to novel secosteroids that show anti-melanoma activity

Synthesis and photochemical transformation of 3β,21-dihydroxypregna-5,7-dien-20-one to novel secosteroids that show anti-melanoma activity

Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3β, 17α, 20-triol and their bioactivity in melanoma cells

Bismuth(III) triflate-catalyzed rearrangement of 16α,17α-epoxy-20-oxosteroids. Synthesis and structural elucidation of new 16α-substituted 17α-alkyl-17β-methyl-Δ13-18-norsteroids

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