Stevioside and Steviol as Starting Materials in Organic Synthesis

Moons, Nico; Borggraeve, Wim M. De; Dehaen, Wim

doi:10.2174/138527212803251703

Cited by 22 publications

(21 citation statements)

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“…Isosteviol has low absorption in the human body in order to increase the bioavailability of the analogues of the said compound were synthesized, which displayed a better performance. In this regard, isosteviol was converted via many reactions into 1,2,4-triazine [ 59 , 168 , 169 ]. The diabetes mellitus also resulted in hyperglycemia, generation of reactive oxygen species (ROS) and also affecting skeletal muscles [ 170 ].…”

Section: Pharmacological Activities Of Isosteviol Derivativesmentioning

confidence: 99%

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

et al. 2019

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Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.

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Section: Pharmacological Activities Of Isosteviol Derivativesmentioning

confidence: 99%

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

et al. 2019

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“…Steviol exhibits a kaurene diterpenoid structure, similar to that of gibberellin (3). Its rearrangement product isosteviol and steviol itself have been used as starting reagents for synthetic medicines (4). The acceptable daily intake of steviol is 4 mg/kg body weight/day (5) and its median lethal dose (LD 50 ) value is 15 g/kg body weight in rats and mice, irrespective of the gender (3).…”

Section: Introductionmentioning

confidence: 99%

The natural sweetener metabolite steviol inhibits the proliferation of human osteosarcoma U2OS cell line

et al. 2018

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Steviol is the colonic metabolite of the natural sweetener steviol glycosides. It does not diffuse to the blood and the half maximal inhibitory concentration of steviol is longer compared with that of current chemotherapy agents, including 5-fluorouracil and doxorubicin. The present study demonstrated that steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner, and that the inhibition rate is comparative with that of doxorubicin and 5-fluorouracil. The mechanism of this anticancer activity is also investigated. The results indicated that steviol inhibits U2OS cells through inducing G1 phase cell cycle arrest, downregulating the ability of colony formation via a mitochondrial apoptotic pathway, which was indicated by an increase of the Bax/Bcl-2 ratio and activation of cyclin-dependent kinase inhibitor 1, tumor protein 53 and cyclin-dependent kinase; whereas a Survivin and Caspase 3-independent mechanism was involved. Considering that steviol appears minimally in the plasma during metabolism, and possesses a median lethal dose of 100-fold greater compared with that of 5-fluorouracil, it may become a potential chemotherapy agent.

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“…This is despite the fact that dihydroxy-substituted diterpene alkaloids as formal aminodiols with diverse pharmacological activity, owing to both basic nitrogen incorporated into their ring system and separated hydroxyl groups, have been thoroughly studied [22,23]. From this point of view, steviol, the aglycon of natural artificial sweetener stevisoide (isolated from the extract of the Paraguayan shrub Stevia rebaudiana L.) [24], has proved to be excellent starting material for the synthesis of ent-kaurane diterpenoids [25], with a wide range of biological activity (Figure 1), such as cytotoxic and apopthosis (I-III) [26][27][28][29], or glutathione S-transferase-inducing activity [30]. Some steviol derivatives that have substituted the carboxylic function with an amino group at the C-4 position possess inhibitory effects against Hepatitis B virus (Figure 1, IV) [31].…”

Section: Int J Mol Sci 2020 20 X For Peer Review 2 Of 20mentioning

confidence: 99%

“…Some steviol derivatives that have substituted the carboxylic function with an amino group at the C-4 position possess inhibitory effects against Hepatitis B virus (Figure 1, IV) [31]. In recent years, several reviews have disclosed thorough discussions about the syntheses of steviol-based polyols [28,32], or even more complex structures [25,33,34]. It is important to note that, in most cases, acid sensitivity and the rapid rearrangement of the ent-kaurane ring system were mentioned as the limitation of transformations.…”

Section: Int J Mol Sci 2020 20 X For Peer Review 2 Of 20mentioning

confidence: 99%

Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpen Aminodiols

Nagy

Zupkó

Szakonyi

2019

IJMS

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A library of steviol-based trifunctional chiral ligands was developed from commercially available natural stevisoide and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The key intermediate steviol methyl ester was prepared according to literature procedure. Depending on the epoxidation process, both cis- and trans-epoxyalcohols were obtained. Subsequent oxirane ring opening with primary and secondary amines afforded 3-amino-1,2-diols. The ring opening with sodium azide followed by a “click” reaction with alkynes resulted in dihydroxytriazoles. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. The resulting steviol-type aminodiols were tested against a panel of human adherent cancer cell lines (A2780, SiHa, HeLa, and MDA-MB-231). It was consistently found that the N-benzyl substituent is an essential part within the molecule and the ring closure towards N-benzyl substituted oxazolidine ring system increased the antiproliferative activity to a level comparable with that of cisplatine. In addition, structure–activity relationships were examined by assessing substituent effects on the aminodiol systems.

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Stevioside and Steviol as Starting Materials in Organic Synthesis

Cited by 22 publications

References 0 publications

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

The natural sweetener metabolite steviol inhibits the proliferation of human osteosarcoma U2OS cell line

Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpen Aminodiols

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