Revisiting the reaction of β-chloroacroleins with 2-aminophenol: a new observation

Bera, Rasajit Kumar; Dhananjaya, G.; Singh, Sukhpreet; Ramu, B.; Kiran, Sai Uday; Kumar, Pramod; Mukkanti, K.; Pal, Manojit

doi:10.1016/j.tet.2007.10.101

Cited by 27 publications

(11 citation statements)

References 14 publications

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“…Our interest in the preparation of structurally diverse heterosteroids lead to a need for a facile flexible strategy, in which a common intermediate can be used in a conjunctive fashion to form an array of N -heterocycles attached or fused to the steroid core. Hence, we turned to β-chlorovinyl aldehydes, which are readily available by the Vilsmeier–Haack reaction (Tasneem, 2003 ) and proved to be highly reactive ambident electrophiles (Bera et al, 2008 ; Bezboruah et al, 2013 ; Brockmeyer et al, 2014 ; Kroger et al, 2015 ). Recently, we have reported the synthesis of steroidal pyridazines (Komkov et al, 2015 ; Volkova et al, 2016 ), thiadiazoles (Zavarzin et al, 2013 ), and 4,5-disubstituted pyrimidines (Komendantova et al, 2017 ) via condensation of β-chlorovinyl aldehydes with bis-nucleophiles such as oxamic acid thiohydrazides and amidines.…”

Section: Resultsmentioning

confidence: 99%

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

et al. 2018

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Most breast and prostate tumors are hormone-dependent, making it possible to use hormone therapy in patients with these tumors. The design of effective endocrine drugs that block the growth of tumors and have no severe side effects is a challenge. Thereupon, synthetic steroids are promising therapeutic drugs for the treatment of diseases such as hormone-dependent breast and prostate cancers. Here, we describe novel series of steroidal pyrimidines and dihydrotriazines with anticancer activities. A flexible approach to unknown pyrimidine and dihydrotriazine derivatives of steroids with selective control of the heterocyclization pattern is disclosed. A number of 18-nor-5α-androsta-2,13-diene[3,2-d]pyrimidine, androsta-2-ene[3,2-d]pyrimidine, Δ1, 3, 5(10)-estratrieno[16,17-d]pyrimidine, and 17-chloro-16-dihydrotriazine steroids were synthesized by condensations of amidines with β-chlorovinyl aldehydes derived from natural hormones. The synthesized compounds were screened for cytotoxicity against breast cancer cells and showed IC50 values of 7.4 μM and higher. Compounds were tested against prostate cancer cells and exhibited antiproliferative activity with IC50 values of 9.4 μM and higher comparable to that of cisplatin. Lead compound 4a displayed selectivity in ERα-positive breast cancer cells. At 10 μM concentration, this heterosteroid inhibited 50% of the E2-mediated ERα activity and led to partial ERα down-regulation. The ERα reporter assay and immunoblotting were supported by the docking study, which showed the probable binding mode of compound 4a to the estrogen receptor pocket. Thus, heterosteroid 4a proved to be a selective ERα modulator with the highest antiproliferative activity against hormone-dependent breast cancer and can be considered as a candidate for further anticancer drug development. In total, the synthesized heterosteroids may be considered as new promising classes of active anticancer agents.

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Section: Resultsmentioning

confidence: 99%

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

et al. 2018

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“…They are stable for storage in solution and do not require any special conditions for preparation. Chlorovinyl aldehydes proved to be highly reactive ambident electrophiles that easily undergo a variety of cyclization reactions, especially with compounds having bis‐nucleophilic properties . Inspired by these previous studies and in continuation of our research on the synthesis of N‐heterocycles, we elaborated a conceptually simple, practical and general methodology for the synthesis of 4,5‐substituted pyrimidines based on the condensation of β‐chlorovinyl aldehydes with amidines under mild conditions.…”

Section: Introductionmentioning

confidence: 99%

Efficient Synthesis of 4‐ and 5‐Substituted 2‐Aminopyrimidines by Coupling of β‐Chlorovinyl Aldehydes and Guanidines

et al. 2017

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A general, practical, and simple synthesis of functionalized 2‐aminopyrimidines starting from β‐chlorovinyl aldehydes and amidines is reported. In the presence of potassium carbonate, various ketones have been efficiently transformed into the pyrimidine derivatives by a two‐step sequence involving the Vilsmeier–Haack reaction followed by a condensation reaction with guanidines. The protocol is distinguished by operational simplicity, inexpensive reagents, and functional‐group tolerance. In many cases, pure solid products can be obtained in high to excellent yields without using column chromatography. The synthetic value of the method was demonstrated by the efficient synthesis of steroidal pyrimidines and a precursor of the antitumor agents Imatinib and Mocetinostat.

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“…However, to the best of our knowledge, there are very few reports in which a medium-sized seven-membered benzoxepin ring is fused to a quinoline unit. In this context, Bera et al [20] described a one-pot method for the synthesis of 6,7-dihydrobenzo[2,3]oxepino[4,5- b ]quinolin-12-ols. However, the report is of episodic character and no efforts have been made to develop a general synthetic approach.…”

Section: Introductionmentioning

confidence: 99%

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

Gao¹,

Lin²,

Li³

et al. 2012

Beilstein J. Org. Chem.

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SummaryAn efficient access to the tetracyclic-fused quinoline systems, 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives 4a–l, is described, involving the intramolecular Friedel–Crafts acylation reaction of 2-(phenoxymethyl)-4-phenylquinoline-3-carboxylic acid derivatives 3a–l aided by the treatment with PPA (polyphosphoric acid) or Eaton’s reagent. The required starting compound (2) was obtained by Friedländer reaction of 2-aminobenzophenone (1) with 4-chloroethylacetoacetate by using CAN (cerium ammonium nitrate, 10 mol %) as catalyst at room temperature. The substrates 3a–l were prepared through one-pot reaction of ethyl 2-(chloromethyl)-4-phenylquinoline-3-carboxylate (2) and substituted phenols. Our developed strategy, involving a three-step route, offers easy access to tetracyclic-fused quinoline systems in short reaction times, and the products are obtained in moderate to good yields.

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Revisiting the reaction of β-chloroacroleins with 2-aminophenol: a new observation

Cited by 27 publications

References 14 publications

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells

Efficient Synthesis of 4‐ and 5‐Substituted 2‐Aminopyrimidines by Coupling of β‐Chlorovinyl Aldehydes and Guanidines

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

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