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. 2025 Jun 19;5(7):3545-3554.
doi: 10.1021/jacsau.5c00574. eCollection 2025 Jul 28.

First Total Synthesis and Bioactivity Study of Dumortierinoside A and Concinnoside D: Two Representative D/E-Ring Simultaneously Functionalized Oleanane-Type Triterpene Saponins

Ge Gao  1   2 , Hui Liu  1 , Xing Zhang  3 , De-Yong Liu  1 , Jin-Xi Liao  1 , Ming-Qing Li  3 , Jian-Song Sun  1   2
Affiliations

First Total Synthesis and Bioactivity Study of Dumortierinoside A and Concinnoside D: Two Representative D/E-Ring Simultaneously Functionalized Oleanane-Type Triterpene Saponins

Ge Gao et al. JACS Au. .

Abstract

Efficient chemical synthesis of D/E-ring-functionalized oleanane-type saponins (DERFOS) is highly challenging in carbohydrate chemistry, but more challenging is the access to D/E-ring simultaneously functionalized oleanane-type saponins (DERSFOSs) by chemical synthesis. Based on the MCEPT glycosylation protocol, the DMNPA group for robust stereocontrol of glycosidic linkages, as well as Yu-modified Schonecker-Baran oxidation, the first total synthesis of dumortierinoside A and concinnoside D, the two representatives of DERSFOSs, was achieved from easily accessible feedstock. The longest linear sequences are 24 and 25 steps (counting from oleanolic acid), with the overall yields being 2.1% and 1.6%, respectively. The established strategies and methods could greatly ease the access not only to DERSFOSs but also to DERFOS. Benefited from the successful syntheses, the cytotoxic effects against a series of cancer cell lines were evaluated, and promising results were recorded. The successful establishment of chemical synthesis approaches toward DERSFOSs will greatly help to break the sample acquisition bottleneck, thus speeding up the process of pharmaceutical applications of valuable natural DERSFOSs and DERFOSs.

Keywords: D/E-ring simultaneously functionalized oleanane-type saponins; MCEPT glycosylation; Schonecker−Baran oxidation; bioactivity; total synthesis.

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Figures

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1
Chemical structures of dumortierinoside A and concinnoside D.
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1. Synthesis of Dumortierigenin Aglycone 13
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2. Synthesis of Dumortierigenin Aglycone 21
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3. Synthesis of Monosaccharide MCEPT Donors
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4. Completion of the Synthesis of Dumortierinoside A (1) and the Corresponding Methyl Ester 43
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5. Synthesis of Acacic Acid Lactone 46
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6. Synthesis of Monosaccharide Latent and Active MCEPT Donors
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7. Assembly of the Trisaccharide Chain of Concinnoside D
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8. Completion of the Synthesis of Concinnoside D (2)
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