Rotenoid interconversion. Synthesis of deguelin from rotenone

Anzeveno, Peter B.

doi:10.1021/jo01328a056

Cited by 36 publications

(28 citation statements)

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“…Two days after the confluence was attained, deguelin was added. The stereospecific deguelin, which was synthesized in three steps from the natural product rotenone and conserves the cis-(7aS,13aS) configuration of the natural product, was used (28). The synthetic material conformed to the natural product as evidenced by identical 1 H and 13 C nuclear magnetic resonance, UV-visible, liquid chromatography-mass spectrophotometry, and optical rotation.…”

Section: Methodsmentioning

confidence: 99%

Deguelin-Induced Inhibition of Cyclooxygenase-2 Expression in Human Bronchial Epithelial Cells

Lee

Suh

Kosmeder

et al. 2004

Clinical Cancer Research

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The increased expression of cyclooxygenase (COX)-2 significantly enhances carcinogenesis and inflammatory reactions, and its regulation may be a reasonable target for cancer chemoprevention. We demonstrated previously that deguelin inhibits proliferation of premalignant human bronchial epithelial (HBE) cells, such as 1799 cells and squamous HBE cells, by regulating phosphatidylinositol-3-kinase Akt activity, which is involved in COX-2 expression. We sought to determine the effect of deguelin on COX-2 expression in squamous HBE cells. Deguelin strongly inhibited COX-2 expression in squamous HBE cells, without affecting the COX-1 protein level. Deguelin inhibited proliferation of a variety of non-small cell lung carcinoma (NSCLC) cell lines through apoptosis and induced Bax expression in the H322 NSCLC and squamous HBE cells. Deguelin treatment did not affect Bcl-2 protein levels but increased expression levels of the proapoptotic protein p53 and the cyclin-dependent kinase inhibitors p21 and p27 in the squamous HBE cells. The sensitivity of the squamous HBE and NSCLC cells to deguelin and the inhibitory effects of deguelin on COX-2 expression in the squamous HBE cells indicate that regulation of COX-2 expression is involved in the chemopreventive action of deguelin in lung cancer.

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Section: Methodsmentioning

confidence: 99%

Deguelin-Induced Inhibition of Cyclooxygenase-2 Expression in Human Bronchial Epithelial Cells

Lee

Suh

Kosmeder

et al. 2004

Clinical Cancer Research

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“…The conversion of rot-2′-enonic acid 5 into deguelin 1 was achieved following Anzeveno's method. 9 Finally, the transformation of deguelin 1 into tephrosin 2 was accomplished using a highly diastereoselective chromium-mediated hydroxylation, for which an Étard-like reaction mechanism is tentatively proposed. 12 b Our syntheses provide deguelin 1 and tephrosin 2 in 56% and 42% yield respectively, involve only two chromatographic purifications and allow gram quantities of valuable enantiopure materials to be prepared simply and efficiently, facilitating biological studies thereof.…”

Section: Discussionmentioning

confidence: 99%

“…9 On the basis of Crombie's studies on the diastereoselective chromium-mediated hydroxylation of rotenone 3 to rotenolone 4 , 5 b we reasoned that an analogous hydroxylation of deguelin 1 with potassium dichromate in aqueous acetic acid would provide tephrosin 2 .…”

Section: Introductionmentioning

confidence: 99%

Stereocontrolled semi-syntheses of deguelin and tephrosin

et al. 2017

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“…Deguelin was manufactured from the natural product rotenone (Sigma-Aldrich, Milwaukee, WI) via four steps, as described previously (Anzenveno, 1979). The final product was more than 98% pure.…”

Section: Methodsmentioning

confidence: 99%

Antiangiogenic Effect of Deguelin on Choroidal Neovascularization

Kim¹,

Kim²,

Yu³

et al. 2007

J Pharmacol Exp Ther

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Age-related macular degeneration is the leading cause of blindness in the elderly. Choroidal neovascularization (CNV) leads to severe vision loss in patients of age-related macular degeneration. Previously, we have demonstrated that deguelin, isolated from plants in the Mundulea sericea family, is a chemopreventive agent. This study evaluates the antiangiogenic effect of deguelin on CNV. The toxicity of deguelin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human umbilical vein endothelial cells (HUVECs) as well as histological examination and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining in the deguelin-injected retina. Antiangiogenic activity of deguelin was evaluated by in vitro tube formation assay of HUVECs and in vivo angiogenesis of chick chorioallantoic membrane (CAM). In C57BL/6 mice with laser-induced CNV, deguelin or phosphate-buffered saline was injected intravitreously. CNV lesions were examined by fluorescence angiography and vessel counting in cross-sections. Deguelin showed no effect on cell viability of HUVECs and no retinal toxicity in a concentration range of 0.01 to 1 M. Deguelin effectively inhibited in vitro tube formation of HUVECs and in vivo angiogenesis of CAM. Interestingly, deguelin significantly reduced CNV and its leakage in mouse model of laser photocoagulation-induced CNV. Our data suggests that deguelin is a potent inhibitor of CNV and may be applied in the treatment of other vasoproliferative retinopathies such as retinopathy of prematurity and diabetic retinopathy.

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Rotenoid interconversion. Synthesis of deguelin from rotenone

Cited by 36 publications

References 0 publications

Deguelin-Induced Inhibition of Cyclooxygenase-2 Expression in Human Bronchial Epithelial Cells

Deguelin-Induced Inhibition of Cyclooxygenase-2 Expression in Human Bronchial Epithelial Cells

Stereocontrolled semi-syntheses of deguelin and tephrosin

Antiangiogenic Effect of Deguelin on Choroidal Neovascularization

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