A new, practical synthesis of 2-methoxyestradiols

Rao, P. Nageswara; Cessac, James W.

doi:10.1016/s0039-128x(02)00065-x

Cited by 27 publications

(16 citation statements)

References 15 publications

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“…Friedel-Crafts regioselective ortho -acetylation of the aromatic ring of estradiol 3-methyl ether ( 2 ), obtained from its precursor 1 by simple reduction, was carried out under mild conditions using a one-pot procedure, further developing the available literature method [ 37 ] ( Scheme 1 ). Estradiol was previously reported to undergo diacetylation during treatment with acetyl chloride (AcCl), and AlCl 3 was found not to be a strong enough Lewis acid to initiate a Fries rearrangement of the resulting diacetate to compound 4 ; thus, the more expensive and moisture-sensitive ZrCl 4 had to be used [ 38 , 39 ]. However, it was also demonstrated by Bubert et al that the acetylation could be performed in the presence of AlCl 3 without difficulty when the phenolic OH of estradiol was protected as a methyl ether ( 2 ) [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

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Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds

et al. 2020

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Although the hormone independent cytotoxic activity of several estradiol derivatives endowed with a simple substituent at C-2 has been reported so far, 2-heterocyclic and 2,3-condensed analogs are less investigated from both synthetic and pharmacological points of view. Therefore, novel A-ring-connected 2-pyrazoles of estradiol and, for comparison, their structurally simplified non-steroidal pairs were synthesized from estradiol 3-methyl ether and 6-methoxy-1,2,3,4-tetrahydronaphthalene. Friedel-Crafts acetylation of the protected phenolic compounds and subsequent O-demethylation led to ortho-substituted derivatives regioselectively, which were converted to arylhydrazones with phenylhydrazine, 4-tolylhydrazine and 4-chloro-phenylhydrazine, respectively, under microwave conditions. The hydrazones were subjected to cyclization with the Vilsmeier-Haack reagent immediately after preparation and the ring closure/formylation sequence resulted in steroidal and non-steroidal 4′-formylpyrazoles in moderate to good yields. During reductive transformations, 4-hydroxymethyl-pyrazoles were obtained, while oxidative lactonization of the 4-formylpyrazole moiety with the phenolic OH in the presence of the Jones reagent afforded A-ring-integrated pyrazolocoumarin hybrids and related analogs. Steroidal pyrazoles, which were produced as C-17 acetates due to acetylation of C-17 OH during the primary Friedel-Crafts reaction, underwent deacetylation in alkaline methanol to furnish 2-heterocyclic estradiol derivatives. Pharmacological studies revealed the overall and cancer cell-specific cytotoxicity of the derivatives and the half maximal inhibitory concentrations were obtained for the most promising compounds.

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Section: Resultsmentioning

confidence: 99%

“…According to the general procedure, compound 4 (178 mg) was used. Yield ( 5 ): 141 mg (90%, white solid); Mp 189–191 °C (192–195 °C [ 38 ]); Anal. Calcd.…”

Section: Methodsmentioning

confidence: 99%

Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds

et al. 2020

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“…The introduction of an additional double-bond(s) into ring D of 2ME2 enhanced the in vitro antiproliferative activity on the MDA-MB-435 (human breast carcinoma) and SK-OV-3 (ovarian carcinoma) cell lines as compared with the parent molecule [29]. Compounds 4 and 10 were synthesized via well-known transformations from a common precursor 2, available from the 3-benzyloxy analog 1 [30] of 2ME2 (Scheme 1). Interestingly, some unsaturated derivatives 9 and 13, which lack the 17-hydroxy group, were also demonstrated to retain cell growth-inhibitory effects on both endothelial and tumor cells [31,32].…”

Section: Synthesis and Antiproliferative Activity Of Estrane-derived mentioning

confidence: 99%

Synthesis of sex hormone-derived modified steroids possessing antiproliferative activity

Frank

Schneider

2013

The Journal of Steroid Biochemistry and Molecular Biology

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During recent years intensive research has been focused on the synthesis of structurally modified steroid hormones in order to obtain compounds with beneficial biological activity such as cell-growth inhibition. Experimental results have revealed that some steroidal derivatives possess direct cytostatic effect on cancer cells in a hormone receptor-independent manner. After a brief account on the most important biological function and characteristics of the naturally occurring sex hormones in physiological and pathological conditions, structural modifications of estrane and androstane scaffolds are discussed in detail. The review covers literature publications (from 2002 to 2012) relating to the synthesis and antiproliferative activity of semisynthetic sex hormone-derived molecules containing simple or heterocyclic substituents. The compounds reviewed are divided into three main categories according to their sterane framework and the nature of substitution. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".

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“…those depicted in Fig. 1A [31][32][33][34][35][36] and Fig. 1C, 37,38 involve several steps and require protection/deprotection of the phenolic OH group, expensive reagents or harsh conditions, and suffer from selectivity problems that ultimately lead to the nal product in lower yields than route B.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and conversion of primary and secondary 2-aminoestradiols into A-ring-integrated benzoxazolone hybrids and their in vitro anticancer activity

et al. 2021

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A new, practical synthesis of 2-methoxyestradiols

Cited by 27 publications

References 15 publications

Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds

Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds

Synthesis of sex hormone-derived modified steroids possessing antiproliferative activity

Synthesis and conversion of primary and secondary 2-aminoestradiols into A-ring-integrated benzoxazolone hybrids and their in vitro anticancer activity

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