Microwave induced selective enolization of steroidal ketones and efficient acetylation of sterols in semisolid state

Marwah, Padma; Marwah, Ashok; Lardy, Henry A.

doi:10.1016/s0040-4020(03)00207-2

Cited by 30 publications

(16 citation statements)

References 33 publications

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“…Compound 1 (3β,21-Dihydroxypregn-5-en-20-one acetate) was acetylated following a known procedure [36]. A mixture of compound 1 (7.48 g, 20 mmol) and pTSA·H 2 O (76 mg, 0.4 mol) in acetic anhydride (40 ml) was placed in an open glass tube.…”

Section: Methodsmentioning

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: Methodsmentioning

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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“…The acetylation of compound 1 was carried out following a known procedure [19]. A mixture of steroid 1 (3.74 g, 10 mmol) in a small amount of acetic anhydride (20 ml) and catalytic amount of pTSA·H 2 O (38 mg, 0.2 mol) was placed in an open glass tube.…”

Section: Methodsmentioning

confidence: 99%

A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity

Kim

Chen

et al. 2010

Steroids

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The new steroidal 5,7-diene, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid (17-COOH-7DA), was synthesized from 21-acetoxypregnenolone, with the oxidative cleavage of the side chain being dependent on the presence of oxygen. In human epidermal (HaCaT) keratinocytes, 17-COOH-7DA inhibited proliferation in a dose-dependent manner, starting at a dose as low as 10 −11 M. This inhibition was accompanied by decreased expression of epidermal growth factor receptor, bcl2 and cyclin E2 mRNAs and by increased expression of involucrin mRNA. Inhibition of proliferation was associated with slowing of the cell cycle in G1/G0 phases but not with cell death. 17-COOH-7DA was significantly more potent than pregnenolone, 17-COOH-pregnenolone, 17-COOCH 3 -7DA and calcitriol. 17-COOH-7DA also inhibited proliferation of normal human epidermal melanocytes and human and hamster melanoma lines, however, with lower potency than for keratinocytes. In normal human dermal fibroblasts 17-COOH-7DA stimulated proliferation in serum-free media but inhibited it in the presence of 5% serum. 17-COOH-7DA inhibited cell colony formation of human and hamster melanoma cells, and induced monocyte-like differentiation of human HL60 leukemia cells. Thus, the new steroidal 5,7-diene, 17-COOH-7DA, can serve as an inhibitor of proliferation of normal keratinocytes and normal and malignant melanocytes, as a condition-dependent regulator of fibroblast proliferation and a stimulator of leukemia cell differentiation.

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“…The acetylation of 17α-acetoxy-pregnenolone 1 was carried out following a known procedure 23. Yield: 95%.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives

Żmijewski

Zjawiony

et al. 2008

Photochem Photobiol Sci

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Calcitriol (3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-trien-1α,3β,25-triol) is a powerful oncostatic form of vitamin D3 that is of limited clinical utility due to hypercalcemic (toxic) effects. Since the removal of the side chain reduces or eliminates the calcemic activity of vitamin D3, secosteroidal compounds lacking or with a shortened side chain are good candidates for anti-cancer drugs. In addition, 5,7-steroidal dienes without a side chain can be generated in vivo under pathological conditions. A series of androsta-and pregna-5,7-dienes was efficiently synthesized from their respective 3-acetylated 5-en precursors by bromination-dehydrobromination and deacetylation reactions. Ultraviolet B (UVB) irradiation was used to generate corresponding 9,10-secosteroids with vitamin D-like structures. Additional products with tachysterol-like (T-like) structures or 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol, L-like) were also detected. Different doses of UVB resulted in formation of various products. At low doses, previtamin D-, T-or L-like compounds were formed as the main products, while higher doses induced further isomerization, with formation of potentially oxidized derivatives. In summary, we describe dynamic UVB induced conversion of androsta-and pregna-5,7-dienes into vitamin D-like compounds and their rearranged analogues; additionally novel T-like and L-like structures were also produced and characterized. Further biological evaluation of newly synthesized compounds should help to select the best candidate(s) for potential treatment of hyperproliferative diseases including cancer.

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Microwave induced selective enolization of steroidal ketones and efficient acetylation of sterols in semisolid state

Cited by 30 publications

References 33 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

A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity

Synthesis and photo-conversion of androsta- and pregna-5,7-dienes to vitamin D3-like derivatives

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