Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid

Huang, Xiaochao; Wang, Meng; Pan, Ying‐Ming; Yao, Guiyang; Wang, Hengshan; Tian, Xiaofeng; Qin, Jiang-Ke; Zhang, Ye

doi:10.1016/j.ejmech.2013.08.055

Cited by 83 publications

(31 citation statements)

References 22 publications

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“…General synthetic pathways and reactions described in this work moaniline (158 µL, 1.0 mmol) and triethylphosphite (168 µL, 1.1 mmol) to obtain white crystalline compound 4a 34g (342 mg, 93% yield). 1…”

Section: Diethyl (((3-bromophenyl)amino)(phenyl)methyl)phosphonate (4a)mentioning

confidence: 99%

“…M.p. 185-187 °C; 1 (m, 1H), 4.09-3.96 (m, 4H), 1.34 (t, J = 4.0 Hz, 3H), 1.26 (t, J = 8.0 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 153.0, 151. 1, 148.6, 138.6, 133.8, 129.9, 124.7, 122.9 (2C), 118.9, 115.…”

Section: Diethyl (((2-fluorophenyl)amino)(3-nitrophenyl) Methyl)phospmentioning

confidence: 99%

“…The α-aminophosphonates are core structural components of many pharmacologically active molecules exhibiting diverse range of biological activities such as anticancer, HIV protease inhibitors, and serve as surrogates of α-amino acids. [1][2][3] The Pudovik reaction 4 and Kabachnik-Fields reactions 5 involving nucleophilic addition of phosphite to imines are the most widely used methods for the synthesis of α-aminophosphonates. The aminophosphonates can also be synthesised via acid-catalyzed (Lewis/ Brønsted), 6,7 catalyst-free, 8 microwave assisted 9 condensation of H-phosphonates with aldehydes or imines.…”

Section: Introductionmentioning

confidence: 99%

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Photo-Oxidation Coupled Kabachnik–Fields and Bigenelli Reactions for Direct Conversion of Benzyl alcohols to α-Aminophosphonates and Dihydropyrimidones

Ali¹,

Dangroo²,

Raheem³

et al. 2020

ACSi

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A tandem one-pot solvent free approach for the direct conversion of benzyl alcohols to α-amino phosphonates and dihydropyrimidones is reported. The method relies on a metal free photo-oxidation of benzyl alcohols to benzaldehydes under UV irradiation using ammonium perchlorate followed by Kabachnik-Fields and Biginelli reactions. The reaction conditions are moderate and metal free with good substrate scope. The control experiments were performed to investigate the role of the ammonium perchlorate and molecular oxygen as oxidants. The quenching experiments in the presence of TEMPO and other radical quenchers suggest radical based mechanism.

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Section: Diethyl (((3-bromophenyl)amino)(phenyl)methyl)phosphonate (4a)mentioning

confidence: 99%

Section: Diethyl (((2-fluorophenyl)amino)(3-nitrophenyl) Methyl)phospmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Photo-Oxidation Coupled Kabachnik–Fields and Bigenelli Reactions for Direct Conversion of Benzyl alcohols to α-Aminophosphonates and Dihydropyrimidones

Ali¹,

Dangroo²,

Raheem³

et al. 2020

ACSi

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“…Recently, dehydroabietylamine (also called leelamine), abietic acid, and their synthetic derivatives have been studied for potential anti-cancer activity (Huang et al, 2013; Kuzu et al, 2014; Robertson et al, 2014). Some of these compounds exhibited potent melanoma cell killing activity, while others had a negligible effect (Robertson et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity

Sadashiva

Gowda

et al. 2015

Experimental Parasitology

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Malaria caused by the Plasmodium parasites continues to be an enormous global health problem owing to wide spread drug resistance of parasites to many of the available antimalarial drugs. Therefore, development of new classes of antimalarial agents is essential to effectively treat malaria. In this study, the efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic acid, and their synthetic derivatives was assessed for antimalarial activity. Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N-benzyl derivatives showed excellent activity against P. falciparum parasites with IC50 values of 0.36–2.6 μM. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100 μM) to mammalian cells; thus, this compound can be an important antimalarial drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50 value of ~82 μM. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of ~8.2 to ~13.3 μM. These results suggest that a detailed understanding of the structure–activity relationship of abietane diterpenoids might provide strategies to exploit this class of compounds for malaria treatment.

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“…These well-studied pharmacophores appear in a large number of pharmaceuticals including antibiotic, [8] antiviral [9] and antitumor compounds. [10] Our laboratories recently became interested in these molecules for single molecule enzymatic and biosynthesis experiments. As we required large quantities of such compounds, a rapid continuous flow approach was developed.…”

mentioning

confidence: 99%

Harnessing Thin‐Film Continuous‐Flow Assembly Lines

Britton

Castle

Weiss

et al. 2016

Chemistry A European J

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Inspired by nature’s ability to construct complex molecules through sequential synthetic transformations, we have developed an assembly line synthesis of α-aminophosphonates. In this approach, simple starting materials are continuously fed through a thin-film reactor where the intermediates accrue molecular complexity as they progress through the flow system. Flow chemistry allows rapid multi-step transformations to occur via reaction compartmentalization, an approach not amenable to using conventional flasks. Thin film processing can also access facile in situ solvent exchange to drive reaction efficiency, and through this method, α-aminophosphonate synthesis requires only 443 s residence time to produce 3.22 g h−1. Assembly line synthesis allows unprecedented reaction flexibility and processing efficiency.

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Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid

Cited by 83 publications

References 22 publications

Photo-Oxidation Coupled Kabachnik–Fields and Bigenelli Reactions for Direct Conversion of Benzyl alcohols to α-Aminophosphonates and Dihydropyrimidones

Photo-Oxidation Coupled Kabachnik–Fields and Bigenelli Reactions for Direct Conversion of Benzyl alcohols to α-Aminophosphonates and Dihydropyrimidones

A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity

Harnessing Thin‐Film Continuous‐Flow Assembly Lines

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