A facile and efficient synthesis of 4β-aminopodophyllotoxins

Yu, Yongping; Chen, Shao-Yuan; Wang, Yanguang; Chen, Yaozu

doi:10.1016/s0040-4039(99)00125-2

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…Both 9 and 10 were then reduced under hydrogen atmosphere with Pd/C catalyst to yield the key intermediate 4β-amino congeners 11 and 12 , respectively, in excellent yields. 22 Next, intermediates 11 and 12 were coupled with various sulfonylcarbamates in dry toluene to afford the desired 4β-sulfonylurea podophyllotoxins 13a–l and 14a–e , respectively, in good yields.…”

Section: Resultsmentioning

confidence: 99%

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Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Zhang

Tian

Wang

et al. 2014

Bioorganic & Medicinal Chemistry

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Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC50: 1.41–1.76 μM) and 14e (IC50: 1.72–2.01 μM) showed superior cytotoxic activity compared with etoposide (IC50: 2.03– >20μM), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4′-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin’s 4β position can significantly improve cytotoxic activity.

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Section: Resultsmentioning

confidence: 99%

“…27,28 The key intermediate 4β-amino congeners 11, 12 and 20 were synthesized by our previously reported procedures, and their structures confirmed by direct comparison with an authentic sample and previously reported spectroscopic data. 21,22 …”

Section: Methodsmentioning

confidence: 99%

Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Zhang

Tian

Wang

et al. 2014

Bioorganic & Medicinal Chemistry

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“…Briefly, the precursor 4β-aminoepipodophyllotoxin ( 9 ) was prepared stereoselectively from 1 through azidation and catalytic hydrogenation according to a previously reported method [32]. Next, compound 9 was converted to 4β-formamido-4-deoxypodophyllotoxin ( 10 ) in excellent yield by reaction with ethyl formate under both classical and ultrasonic conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Podophyllotoxin ( 1 ) was isolated from the Chinese medicinal herb Juniperus sabina Linnaeus, and served as the starting material for preparation of all new derivatives. The precursor 4β-aminoepipodophyllotoxin ( 9 ) was synthesized by our previously reported procedures, and its structure was confirmed by direct comparison with an authentic sample and previously reported spectroscopic data [32]. …”

Section: Methodsmentioning

confidence: 99%

Toward synthesis of third-generation spin-labeled podophyllotoxin derivatives using isocyanide multicomponent reactions

Kou

Wang

et al. 2014

European Journal of Medicinal Chemistry

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Spin-labeled podophyllotoxins have elicited widespread interest due to their far superior antitumor activity compared to podophyllotoxin. To extend our prior studies in this research area, we synthesized a new generation of spin-labeled podophyllotoxin analogs via isocyanide multicomponent reactions and evaluated their cytotoxicity against four human cancer cell lines (A-549, DU-145, KB and KBvin). Most of the compounds exhibited potent cytotoxic activity against all four cell lines, notably against the drug resistant KBvin cancer cell line. Among the new analogs, compounds 12e (IC50: 0.60–0.75 µM) and 12h (IC50: 1.12–2.03 µM) showed superior potency to etoposide (IC50: 2.03 – >20 µM), a clinically available anticancer drug. With a concise efficient synthesis and potent cytotoxic profiles, compounds 12e and 12h merit further development as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidates.

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“…Another method has been reported with HN 3 =Et 2 O-BF 3 at À15 C and reduction with SmI 2 in t-BuOK or FeSO 4 =NH 3 . [27,28] Besides the necessary chromatographic purification of both azido epimers, [29] the drawbacks of these methods were (1) the risk of using an azido derivative, potentially explosive, during large-scale synthesis and (2) the cost of a catalytic reduction step. We present here our results to overcome these problems.…”

mentioning

confidence: 99%

Practical Demethylation of Podophyllotoxin and Efficient Preparation of 4-Amino-4-deoxy-4′-demethylepipodophyllotoxin

Guminski

Grousseaud

Cugnasse

et al. 2012

Synthetic Communications

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A facile and efficient synthesis of 4β-aminopodophyllotoxins

Cited by 8 publications

References 12 publications

Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

Toward synthesis of third-generation spin-labeled podophyllotoxin derivatives using isocyanide multicomponent reactions

Practical Demethylation of Podophyllotoxin and Efficient Preparation of 4-Amino-4-deoxy-4′-demethylepipodophyllotoxin

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