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Ageing is a crucial risk factor for the development of age‐related cardiovascular diseases. Therefore, the molecular mechanisms of ageing and novel anti‐ageing interventions need to be deeply studied. Alginate oligosaccharide (AOS) possesses high pharmacological activities and beneficial effects. Our study was undertaken to investigate whether AOS could be used as an anti‐ageing drug to alleviate cardiac ageing. D‐galactose (D‐gal)‐induced C57BL/6J ageing mice were established by subcutaneous injection of D‐gal (200 mg·kg‐1·d‐1) for 8 weeks. AOS (50, 100 and 150 mg·kg‐1·d‐1) were administrated intragastrically for the last 4 weeks. As a result, AOS prevented cardiac dysfunction in D‐gal‐induced ageing mice, including partially preserved ejection fraction (EF%) and fractional shortening (FS%). AOS inhibited D‐gal‐induced up‐regulation of natriuretic peptides A (ANP), brain natriuretic peptide (BNP) and ageing markers p53 and p21 in a dose‐dependent manner. To further explore the potential mechanisms contributing to the anti‐ageing protective effect of AOS, the age‐related mitochondrial compromise was analysed. Our data indicated that AOS alleviated D‐gal‐induced cardiac ageing by improving mitochondrial biogenesis, maintaining the mitochondrial integrity and enhancing the efficient removal of impaired mitochondria. AOS also decreased the ROS production and oxidative stress status, which, in turn, further inhibiting cardiac mitochondria from being destroyed. Together, these results demonstrate that AOS may be an effective therapeutic agent to alleviate cardiac ageing. [ABSTRACT FROM AUTHOR]

An effective and stereoselective protocol for convergent synthesis of solamargine, a representative of spirosolane-type glycoalkaloids, is reported. HB(C6F5)4-catalyzed coupling of 26-azido-pseudodiosgenin with chacotriosyl trichloroacetimidate as the key step for synthesis of solamargine proceeded in high yield and with excellent stereoselectivity. Three analogues of solamargine were synthesized by the method. Protonation of the nitrogen atom by deuterium chloride had a significant influence on the 1H NMR spectrum of solamargine. On the basis of these results, the structure of 16- epi-solamargine was revised to solamargine hydrochloride. The cytotoxicity of solamargine together with its analogues against cancer cell lines was evaluated. [ABSTRACT FROM AUTHOR]

Myrmekioside A, which was isolated from the marine sponge Myrmekioderma sp. as a member of the family of natural mono-O-alkyl-diglycosylglycerols, and which has a strong reversion effect on the tumor cell morphology of ras-transformed cells at 5 μg/mL, was synthesized for the first time in 17 steps and 14% overall yield. The β-glycosidic linkages in myrmekioside A were successfully constructed by the neighbouring-group-participation approach using trichloroacetimidates and thioglycosides as glycosyl donors. The 2R absolute configuration at C-2 of the glycerol backbone was derived from (S)-1,2-isopropylideneglycerol (8). This synthetic approach may be applicable to the preparation of other myrmekioside analogues featuring different sugars and alkyl chains for further structure-activity relationship studies. [ABSTRACT FROM AUTHOR]

A highly efficient and practical total synthesis of the sulfated ganglioside SM1a, a kind of human epithelial carcinoma antigen identified in mammalian kidney, has been accomplished for the first time. The characteristic sequence of SM1a, β- D-Gal p-(1→3)-β- D-NHAcGal p-(1→4)-β- D-(3- O-sulfate)-Gal p-(1→4)-β- D-Glc p-ceramide was assembled by a [3+2] convergent approach. A key trisaccharide building block was formed from a new galactose acceptor 7 containing a potential sulfated site, GalNHTroc donor 6, and galactose donor 4. The cyclic glucosyl ceramide was glycosylated with trisaccharide trichloroacetimidate 2 to give the protected ganglioside backbone in good yield. Selective sulfonation at the 3-OH of the Gal residue followed by global deprotection gave the target molecule SM1a. [ABSTRACT FROM AUTHOR]