First Synthesis of a Series of New Natural Glucosides.

Qu, Mengnan; Zhou, Ling; Cao, Xiao‐Ping

doi:10.1002/chin.200710209

Cited by 1 publication

(2 citation statements)

References 6 publications

(15 reference statements)

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“…To a cooled (0 °C) solution of the known trans - m -propenyl guaiacol ( 6 ; 31 867 mg, 5.28 mmol) in dry DMF (13 mL, 0.4 M) were added NaH (60% dispersion in mineral oil, 304 mg, 7.92 mmol) and BnBr (0.63 mL, 5.28 mmol). The reaction mixture was allowed to warm to 25 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The synthesis of MA02 started with the preparation of tosylate 10 and α-bromoketone 12 for coupling reactions (Scheme 1). Benzyl (Bn)-protection of the known trans-m-propenyl guaiacol (6) 31 followed by asymmetric dihydroxylation 32 of 7 provided diol 8. Selective DDQoxidation of the benzylic hydroxyl group of 9 followed by tosylation successfully afforded 10. α-Bromoketone 12 was prepared by treatment of the commercially available 3′,4′dimethyoxyacetophenone (11) with Br 2 .…”

Section: ■ Introductionmentioning

confidence: 99%

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Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition

Kwon

Lee

Weitzel³

et al. 2015

J. Med. Chem.

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To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from Saururus cernuus, manassantins A (1) and B (2) are potent inhibitors of HIF-1 activity. To define the structural requirements of manassantins for HIF-1 inhibition, we prepared and evaluated a series of manassantin analogues. Our SAR studies examined key regions of manassantin’s structure in order to understand the impact of these regions on biological activity and to define modifications that can lead to improved performance and drug-like properties. Our efforts identified several manassantin analogues with reduced structural complexity as potential lead compounds for further development. Analogues MA04, MA07, and MA11 down-regulated hypoxia-induced expression of the HIF-1α protein and reduced the levels of HIF-1 target genes, including cyclin-dependent kinase 6 (Cdk6) and vascular endothelial growth factor (VEGF). These findings provide an important framework to design potent and selective HIF-1α inhibitors, which is necessary to aid translation of manassantin-derived natural products to the clinic as novel therapeutics for cancers.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%