Hindered Rotation in Arylnaphthalene Lignans

Charlton, James L.; Oleschuk, Curtis J.; Chee, Gaik‐Lean

doi:10.1021/jo952048e

Cited by 84 publications

(69 citation statements)

References 17 publications

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“…8 These atropisomers interconvert slowly, hence permitting the two diastereomers observed in the NMR spectra, but the rotation barrier is too small for the individual diastereomers to be isolated at room temperature. 37 Compound 2 was isolated as an amorphous, colorless powder. The similar UV and IR spectra to those of 1 indicated that 2 is also an arylnaphthalene lignan lactone.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei

Ren¹,

Lantvit²,

Deng³

et al. 2014

Planta Med

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Two new (1 and 2) and four known arylnaphthalene lignan lactones (3−6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O- [(2,3,4- (7) found to be the most potent, exhibiting IC 50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase IIα activity. C ancer is a serious threat to human health, and the discovery and development of promising new agents to treat this condition is therefore an urgent need. Natural products and their semisynthetic derivatives are used widely in cancer chemotherapy.1,2 As an example, etoposide (VP-16) is a semisynthetic aryltetralin lignan lactone glycoside modeled on the natural product podophyllotoxin. It targets DNA topoisomerase II (topo II) and has been utilized for decades to treat several types of cancer.3 However, side effects have been reported for etoposide, including myelosuppression and the development of secondary leukemias linked to topo II inhibitory activity. 4 Thus, it is highly desirable to discover new agents to treat cancer showing diverse mechanisms of action.Etoposide is a semisynthetic epipodophyllotoxin glycoside derived from podophyllotoxin that is a naturally occurring aryltetralin lignan lactone containing four stereogenic centers at its C-7, -8, -7′, and -8′ positions. Podophyllotoxin is well known to occur in Podophyllum peltatum and P. emodi var. hexandrum (syn. Sinopodophyllum hexandrum) (Berberidaceae). 3,5,6 The latter plant has been found to contain both aryltetralin and arylnaphthalene lignan lactones. 7 In a manner different from aryltetralin lignan lactones, arylnaphthalene lignan lactones are based on a naphthalene unit rather than a tetrahydronaph-

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Section: ■ Results and Discussionmentioning

confidence: 99%

Potent cytotoxic arylnaphthalene lignan lactones from Phyllanthus poilanei

Ren¹,

Lantvit²,

Deng³

et al. 2014

Planta Med

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“…33 Based upon Charlton's studies, we designed lamellarin analogues (1) and (2) having 1,3-benzodioxol-5-yl group at the C1 position ( Figure 2). These compounds may be suitable for VT NMR experiments, because two substituents R on the 1,3-benzodioxol-5-yl group are diastereotopic each other and, therefore, the chemical shifts of the substituents R in NMR spectra should be different, if rotation around C1-C11 single bond…”

Section: Resultsmentioning

confidence: 99%

Rotational Energy Barrier around the C1–C11 Single Bond in Lamellarins: A Study by Variable-Temperature NMR

Fukuda¹,

Itoyama

Minagawa³

et al. 2014

HETEROCYCLES

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-In order to estimate the free energy barrier to rotation around the C1-C11 single bond in lamellarins, new lamellarin analogues (1a), (1b), (2a), and (2b) possessing diastereotopic protons or carbons at the C1 aryl moiety were synthesized. Variable-temperature 1 H and 13 C NMR measurements of these analogues revealed that the free energy barriers to rotation around the C1-C11axis in 5,6-saturated and 5,6-unsaturated lamellarins were around 72-74 and 83-87 kJ/mol, respectively.

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“…Diphyllin was prepared according to the procedure reported previously. 14) Nextly, hydrazide 1 was obtained as yellow solid in 87% yield by the reaction of diphyllin with excess hydrazine hydrate in ethanol over a 6 h reflux period. The structure of compound 1 was confirmed by mass spectroscopy and H-NMR spectra indicated the chemical shift of the NH 2 proton at dϭ4.46 ppm in the form of singlet peak.…”

Section: Resultsmentioning

confidence: 99%