Concise synthesis of two natural triterpenoid saponins, oleanolic acid derivatives isolated from the roots of Pulsatilla chinensis

doi:10.1016/j.carres.2009.05.011

Carbohydrate Research

Volume 344, Issue 11, 27 July 2009, Pages 1276-1281

https://doi.org/10.1016/j.carres.2009.05.011 Get rights and content

Abstract

The first synthesis of two natural triterpenoid saponins, which were isolated from the roots of Pulsatilla chinensis and exhibited excellent in vitro cytotoxic activity against HL-60 cells, was concisely achieved in a convergent approach. We employed an odourless 2-methyl-5-tert-butylphenyl (Mbp) thioglycoside and trichloroacetimidate donors in one-pot reaction as a key step.

Graphical abstract

Introduction

Triterpenoid saponins, which are widely distributed in plants and in some marine organisms,1, 2, 3, 4 have been reported to present a broad spectrum of well-defined biological and pharmacological activities, including anti-tumour,5, 6, 7, 8, 9, 10, 11, 12 anti-inflammatory,¹³ anti-fungal,14, 15, 16 and anti-HIV.17, 18, 19 Attracted by these interesting biological activities, several research groups have reported on the synthesis of many oleanane-type triterpenoid saponins.20, 21, 22, 23, 24, 25, 26, 27, 28 Notably, the synthesis of β-hederin, hederacolchiside A₁ and its anologues with prominent anti-tumour activity were reported by Cheng and co-workers.29, 30 Recently, we were attracted by two naturally occurring oleanane-type triterpenoid saponins: 3-O-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl]oleanolic acid (1), and, 3-O-{β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyl}oleanolic acid (2) (Fig. 1), which were isolated from the roots of Pulsatilla chinensis by Sashida and co-workers.³¹ These triterpenoid saponins show prominent cytotoxic activity against HL-60 cells with an IC₅₀ of 2.6 and 2.7 μg/mL, respectively.³¹ Herein, we report the synthesis of the two natural saponins.

Section snippets

Results and discussion

The development of various glycosylation methods and sophisticated approaches using protecting group manipulations, especially the development of a ‘one-pot sequential glycosylation’ strategy, has greatly facilitated the synthesis of oligosaccharides and glycoconjugates bearing complicated sugar moieties.32, 33, 34, 35, 36, 37, 38, 39, 40, 41 By applying the ‘one-pot sequential glycosylation’ procedure, Yu and co-workers have successfully completed the synthesis of a group of natural dioscins

General methods

Commercial reagents were used without further purification unless specialized. Solvents were dried and redistilled prior to use in the usual way. Thin-layer chromatography (TLC) was performed on precoated E. Merck Silica Gel 60 F254 plates. Flash column chromatography was performed on silica gel (200–300 mesh, Qingdao, China). Melting points were determined on a Fisher–Johns apparatus and are uncorrected. Optical rotations were determined with a Perkin–Elmer Model 241 MC polarimeter. UV spectra

Acknowledgement

This work was financially supported by the Natural Science Foundation of China (30701046).

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Concise synthesis of two natural triterpenoid saponins, oleanolic acid derivatives isolated from the roots of Pulsatilla chinensis

Abstract

Graphical abstract

Introduction

Section snippets

Results and discussion

General methods

Acknowledgement

Phytochemistry

Carbohydr. Res.

Carbohydr. Res.

Carbohydr. Res.

Carbohydr. Res.

Carbohydr. Res.

Tetrahedron Lett.

Tetrahedron Lett.

Tetrahedron Lett.

Tetrahedron Lett.

Tetrahedron

Carbohydr. Res.

Carbohydr. Res.

Saponins

Saponins Used in Traditional and Modern Medicine

Khim.-Farm. Zh.

Chem. Pharm. Bull.

Chem. Pharm. Bull.

J. Nat. Prod.

J. Nat. Prod.

J. Nat. Prod.

J. Nat. Prod.

J. Nat. Prod.

J. Nat. Prod.

J. Nat. Prod.