Efficient Synthesis of Novel Jolkinolides and Related Derivatives Starting from Stevioside

Shi, Lian Yong; Wu, Jun; Zhang, Da Yong; Wu, Yang; Hua, Wei; Wu, Xiao Ming

doi:10.1055/s-0031-1289293

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…Meanwhile, the preparation of 1 is more problematic, as the degradation reaction described in the literature (Malaprade cleavage [ 30 , 31 , 32 ] with NaIO 4 followed by alkaline hydrolysis) of stevioside gave 1 in only 20–30% yield. Our yield is in excellent agreement with the reported data [ 29 ] of M. Ukiya; previously reported [ 30 , 31 , 32 ] yields ranging between 57 and 70% could not be reproduced in our labs. Alternatively, enzymatic hydrolyses have been described in the literature [ 33 , 34 ], but the enzymes used in these reactions are not commercially available or are difficult to obtain.…”

Section: Resultsmentioning

confidence: 99%

F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance

Heise,

Heisig,

Meier

et al. 2024

Molecules

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Steviol and isosteviol were prepared from the commercially available sweetener stevioside and converted into lipophilic F16 hybrids. Their cytotoxicity was determined in SRB assays and showed to depend on both the substitution pattern of the aromatic substituent as well as on the spacer length. Therefore, compound 25 held an IC50 (A2780) of 180 nM, thus surpassing the activity of comparable rhodamine hybrids. Several of the compounds were also able to overcome drug resistance in the A2780/A2780cis model. Extra staining experiments showed a similar subcellular accumulation pattern of the F16 hybrids as a well-established mitocan, hence proving preferential mitochondrial accumulation but also some other accumulation in other cellular areas.

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Section: Resultsmentioning

confidence: 99%

F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance

Heise,

Heisig,

Meier

et al. 2024

Molecules

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“…Recently, our research group reported a protocol for synthesizing jolkinolide A and jolkinolide B [21]. We also reported the first synthesis of jolkinolide derivatives [22,23]. 19-(Benzyloxy)-19-oxojolkinolide B , one of derivatives we synthesized, showed potential inhibitory effect in different kinds of cancer cell lines.…”

Section: Introductionmentioning

confidence: 94%

“…After jolkinolide derivatives synthesized, comparative molecular field analysis (CoMFA) was employed to establish the 3D-QSAR model to further explain the structure-activity relationships (SAR) of jolkinolide derivatives. For the evaluation of functional groups introduced into the ring A of jolkinolide, we evaluated the 33 derivatives we had synthesized to analyze the impact on the design of jolkinolide derivatives [22,23]. The structures of 33 jolkinolide derivatives were displayed in the S1 Fig.…”

Section: D-qsar Study Of Jolkinolide Derivativesmentioning

confidence: 99%

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19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), an ent-abietane diterpene diepoxide, inhibits the growth of bladder cancer T24 cells through DNA damage

et al. 2021

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Diterpenoids jolkinolide A and B, were first isolated from Euphorbia fischeriana. In our previous research, 19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), a derivative of jolkinolides, was synthesized as a novel ent -abietane diterpene diepoxide. In this study, 19-BJB showed strong in vitro activity against bladder cancer cell lines. DNA damage which was observed through the interaction of 19-BJB with nucleotide chains and affected DNA repair resulted in the activation of checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) in bladder cancer cell lines. In vivo testing in nude mice also proved that 19-BJB revealed a potential inhibitory effect on tumor growth. Additionally, the 3D-QSAR models of jolkinolides were established. Briefly, we proved that 19-BJB could potentially be used as a drug to inhibit the growth of bladder tumor.

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“…Steviol (1) was synthesised from the commercially available natural glycoside stevioside (I) in a two-step reaction as described in the literature [25,26]. For esterification of the steviol, diazomethane was used, resulting in methyl ester 3 in mere minutes without observation of cyclopropanation as a side reaction (Scheme 1) [25].…”

Section: Synthesis Of Key Intermediate β-Keto Alcoholmentioning

confidence: 99%

Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers

Bai,

Schelz,

Boncz

et al. 2023

Molecules

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A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic N-substituted derivatives. The antiproliferative effects were assayed using the MTT method.

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Efficient Synthesis of Novel Jolkinolides and Related Derivatives Starting from Stevioside

Cited by 7 publications

References 9 publications

F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance

F16 Hybrids Derived from Steviol or Isosteviol Are Accumulated in the Mitochondria of Tumor Cells and Overcome Drug Resistance

19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), an ent-abietane diterpene diepoxide, inhibits the growth of bladder cancer T24 cells through DNA damage

Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers

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