First total synthesis of natural pulsatilla saponin D via highly stereospecific glycosylation

Kim, Minkyu; Lim, Eunyoung; Jung, Mankil

doi:10.1016/j.tet.2013.04.095

Cited by 13 publications

(10 citation statements)

References 24 publications

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“…Our results clearly showed that the configuration at the anomeric centre of acceptor significantly influenced the regioselectivity of the glycosylation of 3,4-diols. Acceptors, bearing the axially oriented substituent at the anomeric position (11,12) provided the expected 1/3 linked regioisomers preferrentially. In the case of acceptor 17, in which the aglycon part occupies the equatorial position, the 1/4 linked regioisomers were obtained as slightly preferred products.…”

Section: Influence Of the Hydrogen Bond On The Regioselectivity Of Glmentioning

confidence: 94%

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Study on the synthesis of regio- and stereoisomers of the disaccharide unit of the OSW-1 saponin

Pakulski

Cmoch

2015

Tetrahedron

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Section: Influence Of the Hydrogen Bond On The Regioselectivity Of Glmentioning

confidence: 94%

“…Found: C, 49.67; H, 6.65; N, 2.00.5.2.13. (E,Z)-1-Propenyl 2-O-acetyl-b-L-arabinopyranoside(12). Method A. L-Arabinopyranoside 11 (1.000 g, 4.31 mmol) was converted into 1-propenyl derivative 12 using the procedure described for 8.…”

mentioning

confidence: 99%

Study on the synthesis of regio- and stereoisomers of the disaccharide unit of the OSW-1 saponin

Pakulski

Cmoch

2015

Tetrahedron

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“…13 C-NMR chemical shifts of each sugar component with the correct configuration for the protected compound 9a-i and the anomeric configuration at C-1 of the arabinopyranoside of structures 9a-i was determined to be trans diaxial on the basis of the 13 C- 1 H coupling constants as previously demonstrated. 9) tert-Butyldiphenylsilyl (TBDPS) groups of hederagenins were deprotected by tetra-n-butylammonium fluoride (TBAF). Total deprotection of the trisaccharide moieties of the saponin analogues was accomplished in situ in one step.…”

Section: Resultsmentioning

confidence: 99%

“…8) In addition, we reported total synthesis of Pulsatilla saponin D (PSD). 9) These natural saponin products were obtained in small amounts, which was a limiting factor. Chemical synthesis may resolve this problem, and may easily provide suitable compounds for study of structure-activity relationships (SAR) and for the other studies.…”

Section: ) Saponins With Hederagenin Such As Hederacolchid a {Hederagmentioning

confidence: 99%

“…The anomeric configuration at C-1 of the a rhamnopyranoside of structures 22a-g was determined as trans diaxial on the basis of the 13 C-1 H coupling constants, as previously shown. 9) Then TBDPS groups of hederagenin were again deprotected by TBAF. Total deprotection of disaccharide moieties of saponin analogs 22a-g was accomplished in situ in one step using potassium t-butoxide to afford the rhamnose-cored saponin analogs 23a-g (Chart 4).…”

Section: Chartmentioning

confidence: 99%

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Total Synthesis and Anticancer Activity of Novel <i>Pulsatilla</i> Saponin D Analogues

Kim

Park

Chung

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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Novel saponins that retain a free carboxyl group at the C-17 position and various sugars linked at the C-3 position of hederagenin aglycone were synthesized via stereospecific glycosylation. Since these natural products represented by Pulsatilla saponin D (PSD) were obtained in very small amounts, the total synthesis developed in this paper will resolve this problem of scarcity. The two types of synthesized arabinose-and rhamnose-cored saponins showed potent anticancer activity against a human lung cancer cell line (A549), and most disaccharide moiety saponins possessed more potent anti-lung cancer activity. Among the novel PSD analogues containing disaccharide saponins, compound 10i showed anti-lung cancer activity (6.6 µM) that was four-fold more potent than the clinical agent Iressa ® (26.08 µM). Key wordskalopanaxsaponin A, and sapindoside C have been shown to have potent cytotoxic activities toward various cancer cell lines.2-7) Among hederagenins, Pulsatilla saponin D (PSD) 10 ( Fig. 1) not only displayed strong in vitro anticancer activities, but also more potent in vivo antitumor activities in mice bearing Lewis lung carcinoma, exceeding the effects of even taxol and doxorubicin.8) In addition, we reported total synthesis of Pulsatilla saponin D (PSD). 9) These natural saponin products were obtained in small amounts, which was a limiting factor. Chemical synthesis may resolve this problem, and may easily provide suitable compounds for study of structure-activity relationships (SAR) and for the other studies.2,10) The result of SAR showed saponins with hederagenin retaining the free carboxyl group at the C-17 position had stronger anticancer activity than related compounds with other substituents. The hederagenin derivatives, that have sugar moieties on the C-3 position, also showed potent anticancer activity.11,12) Most isolated PSD analogs maintained derivative with sugars bound at the 2-OH of the arabinose moiety.8) Therefore, we proposed to study the effect of derivatization at 3-OH on the anticancer activity for SAR study. In this paper, we report total synthesis of new PSD analogs with various sugar moieties linked at C-3 position of hederagenin and at 3-OH of arabinose moiety. We also evaluated the in vitro anticancer activity of these new compounds. Results and DiscussionWe designed two types of saponin analogues arabinose-and rhamnose-directly glycosylated hederagenins. Stereospecific glycosylation of the glycosyl acceptor, as illustrated by the arabinose moiety 1, with perbenzoylated trichloroacetimidates donors 1a-d [13][14][15][16] was achieved in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) in dichloromethan (CH 2 Cl 2 ) at −78°C to give disaccharides 2a-d (Chart 1). Then, the acetyl group was removed using acetyl chloride/ CH 3 OH to give compounds 3a-d. 17) Glycosylation of compounds 1a-d with the C-4 free hydroxyl group of compounds 3a-d under the TMSOTf as a promoter at −78°C afforded trisaccharide 4a-g. The hydroxyl groups at the C-3, -4 positions in compound 6 as t...

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Triterpenoid Glycosides

2024

Carbohydrate Chemistry in the Total Synthesis of Naturally Occurring Glycosides

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First total synthesis of natural pulsatilla saponin D via highly stereospecific glycosylation

Cited by 13 publications

References 24 publications

Study on the synthesis of regio- and stereoisomers of the disaccharide unit of the OSW-1 saponin

Study on the synthesis of regio- and stereoisomers of the disaccharide unit of the OSW-1 saponin

Total Synthesis and Anticancer Activity of Novel <i>Pulsatilla</i> Saponin D Analogues

Triterpenoid Glycosides

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