Synthesis of triterpenoid triazine derivatives from allobetulone and betulonic acid with biological activities

The synthetic transformation and modification of natural products with the aim to improve the biological properties is an area of current interest. The triterpenoids betulin and betulinic acid are very abundant in nature and now are commercially available. In our study, starting from betulin and betulinic acid, we obtained allobetulone and betulonic acid in a few synthetic steps. The ketone function at the A-ring was used as the starting point for the synthesis of a series of 1,2,4-triazine-fused triterpenoids. The alkylation and Liebeskind–Srogl coupling were used for further substitution of 1,2,4-triazines, and the intramolecular hetero Diels–Alder reaction leads to interesting fused thienopyridine derivatives. All new compounds were tested for their cytostatic activities against murine leukemia L1210, human cervix carcinoma HeLa and human lymphoblast CEM tumor cells. The results show that some triterpenoid triazine betulonic acid derivatives have a promising cytostatic activity in vitro and could be used as potential leads for the development of new type of anti-cancer agents. Several compounds were also endowed with anti-HCMV activity in the low micromolar range.     

Constituents from the pseudofruits of Hovenia dulcis and their chemotaxonomic significance

Sixteen compounds, including six flavonoids (1–6), one lignan (7), three megastigmanes (8–10), three triterpenoids (11–13), and three benzoic acid derivatives (14–16) were isolated and structurally elucidated from the pseudo-fruits of Hovenia dulcis. Their structures were analyzed by NMR spectroscopic and data comparison. Among them, compounds 4, 7–11, 13, 15, and 16 were isolated from the Hovenia genus for the first time. The chemotaxonomic significance of the isolates was also described, which revealed a relationship between H. dulcis and H. acerbar as well as other species belonging to the Rhamnaceae family.     

Chemical constituents from the fruits of Melia azedarach (Meliaceae)

A new apotirucallane-type triterpenoid, 3α-benzoate triterpenoid A (1), along with six known triterpenoids (2–7), one aromatic ester (8) and eight lignans (9–16), were isolated from the fruits of Melia azedarach Linn. The structure of 1 was determined by spectral analyses, including HR-ESI-MS, 1D NMR (¹H NMR and ¹³C NMR) and 2D NMR (HSQC and HMBC) analyses. 10, 11 and 16 were reported for the first time from the family Meliaceae, 8 was identified from the genus Melia for the first time, and 2, 3, 5, 7, 9 and 12–15 were obtained from M. azedarach for the first time. The chemotaxonomic significance of these compounds is discussed.     

Phytochemical and chemotaxonomic study on the leaves of Rhododendron dauricum L

The phytochemical study of the leaves of Rhododendron dauricum L. (Ericaceae) led to the isolation and identification of 44 compounds, including fourteen triterpenoids (1–14), thirteen flavonoids (15–27), eight phenols (28–35), four grifolin derivatives (36–39), two diterpenoids (40–41), two megastigmanes (42–43) and one sesquiterpenoid (44). The chemical structures of these compounds were identified by spectroscopic data and compared with those previously reported. This is the first report on compounds 25, 31, 34, 40, 43, and 44 from the family Ericaceae, compound 42 from the genus Rhododendron, and compounds 24, 28, 30, 32, 33 and 35 from R. dauricum. The chemotaxonomic significance of these compounds was discussed.     

Compounds from Kadsura angustifolia with anti-HIV activity

Four new cycloartane triterpenoids, angustific acid A (1), angustific acid B (2), angustifodilactone A (3) and angustifodilactone B (4) were isolated from the branches of Kadsura angustifolia together with six known compounds, micranoic acid B (5), nigranoic acid (6), schisandrin (7), schisantherin D (8), interiotherin B (9), schisantherin B (10). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. Compound 1, characterized by the presence of a C-16/C-17, C-20/C-21 conjugated diene and a C-1/C-7 ester bridge formed in rings A and B, provided a novel structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, the anti-HIV activities of these compounds were determined in infected C8166 cells, and it was found that angustific acid A (1) exhibited the most potent anti-HIV activity with an EC₅₀ value of 6.1 μg/mL and a therapeutic index of more than 32.8.     

Antifibrotic constituents of Alnus firma on hepatic stellate cells

Suppression of hepatic stellate cell (HSC) growth and activation have been proposed as therapeutic strategies for the treatment and prevention of liver fibrosis. In the course of screening antifibrotic activity of natural products, the methanolic extract of Alnus firma barks (Betulaceae) showed inhibitory activity of cell proliferation on HSC-T6 cells. A new triterpenoid characterized as lup-20(29) en-2,28-diol-3-yl caffeate (13) was isolated with 12 known diarylheptanoids (1-12) from the barks of A. firma using bioactivity-guided fractionation. Among these compounds, 2 and 13 significantly inhibited the proliferation of HSCs in dose- and time-dependent manners at concentrations from 10 to 100 μM. Taken together, antifibrotic activities of A. firma and its active constituents might suggest the therapeutic potentials against liver fibrosis.     

Structure–activity relationships of lanostane-type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors

A series of lanostane-type triterpenoids, identified as ganoderma alcohols and ganoderma acids, were isolated from the fruiting body of Ganoderma lingzhi. Some of these compounds were confirmed as active inhibitors of the in vitro human recombinant aldose reductase. This paper aims to explain the structural requirement for α-glucosidase inhibition. Our structure–activity studies of ganoderma alcohols showed that the OH substituent at C-3 and the double-bond moiety at C-24 and C-25 are necessary to increase α-glucosidase inhibitory activity. The structure–activity relationships of ganoderma acids revealed that the OH substituent at C-11 is an important feature and that the carboxylic group in the side chain is essential for the recognition of α-glucosidase inhibitory activity. Moreover, the double-bond moiety at C-20 and C-22 in the side chain and the OH substituent at C-3 of ganoderma acids improve α-glucosidase inhibitory activity.These results provide an approach with which to consider the structural requirements of lanostane-type triterpenoids from G. lingzhi. An understanding of these requirements is considered necessary in order to improve a new type of α-glucosidase inhibitor.     

Triterpenoid-biosynthetic UDP-glycosyltransferases from plants

Triterpenoid saponins are naturally occurring structurally diverse glycosides of triterpenes that are widely distributed among plant species. Great interest has been expressed by pharmaceutical and agriculture industries for the glycosylation of triterpenes. Such modifications alter their taste and bio-absorbability, affect their intra?/extracellular transport and storage in plants, and induce novel biological activities in the human body. Uridine diphosphate (UDP)-glycosyltransferases (UGTs) catalyze glycosylation using UDP sugar donors. These enzymes belong to a multigene family and recognize diverse natural products, including triterpenes, as the acceptor molecules. For this review, we collected and analyzed all of the UGT sequences found in Arabidopsis thaliana as well as 31 other species of triterpene-producing plants. To identify potential UGTs with novel functions in triterpene glycosylation, we screened and classified those candidates based on similarity with UGTs from Panax ginseng, Glycine max, Medicago truncatula, Saponaria vaccaria, and Barbarea vulgaris that are known to function in glycosylate triterpenes. We highlight recent findings on UGT inducibility by methyl jasmonate, tissue-specific expression, and subcellular localization, while also describing their catalytic activity in terms of regioselectivity for potential key UGTs dedicated to triterpene glycosylation in plants. Discovering these new UGTs expands our capacity to manipulate the biological and physicochemical properties of such valuable molecules.     

Triterpenoid saponins and C-glycosyl flavones from stem bark of Erythrina abyssinica Lam and their cytotoxic effects.

Six new compounds including two oleanane-type triterpenoid saponins (1, 2) and four C-glycosyl flavones (3–6), along with a known saponin (7), three di-C-glycosyl flavones (8–10) and a glycosyl auronol (11), were isolated from the stem bark of Erythrina abyssinica Lam. The structures of the new compounds, identified as 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucuronopyranosyl]-22-O-β-d-glucopyranosyl sophoradiol (1), 3-O-[α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-β-d-glucuronopyranosyl]-22-O-β-d-glucopyranosyl sophoradiol (2), 6-C-β-glucopyranosyl-8-C-β-quinovopyranosyl apigenin (3), 6-C-β-quinovopyranosyl-8-C-β-glucopyranosyl apigenin (4), 8-C-[6″-O-α-l-rhamnopyranosyl-(1‴ → 6″)]-β-glucopyranosyl 7,4′-dihydroxyflavone (5) and 8-C-[6″-O-β-d-xylopyranosyl-(1‴ → 6″)]-β-glucopyranosyl 7,4′-dihydroxyflavone (6), were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and acid hydrolysis. These new compounds together with the known saponins 7 were evaluated for their cytotoxic activity against MCF-7 (estrogen dependent) and MDA-MB-231 (estrogen independent) cell lines. The new saponin 2 exhibited the highest cytotoxic activity among tested compounds, exerting a selective inhibitory effect against the proliferation of MCF-7 cells, with lower IC₅₀ value (12.90 μM) than that of the positive control, resveratrol (13.91 μM). Structure–activity relationship of these compounds is also discussed.     

冻地银莲花的化学成分

从冻地银莲花(Anemone Tupestris ssp.Gelida (Max.)Lauener)中分离鉴定了12个化合物.分别为常春藤配基(1).刺楸皂甙A(2),牡丹草皂甙B(3),白头翁皂甙D(4),常春藤皂甙B(5),刺楸皂甙B(6),hederacholichiside E(7),hederacholichiside F(8),槲皮素-7-O-α-L-鼠李糖甙(9)槲皮素-3-O-β-D-半乳糖-7-O-α-L-鼠李糖甙(10).胡萝卜甙(11)和β-谷甾醇(12).以上化合物在本植物中均为首次报道.