Isolation of Glycosidase-Inhibiting Hyacinthacines and Related Alkaloids from Scilla socialis

Abstract

An examination of the bulbs of Scilla socialis has resulted in the isolation of 11 hyacinthacines, two pyrrolidines, and three piperidines. The structures of the new alkaloids were elucidated by spectroscopic methods as beta-1-C-ethyldeoxymannojirimycin (5), hyacinthacines B7 (10), C2 (11), C3 (12), C4 (13), and C5 (14), and alpha-5-C-(3-hydroxybutyl)hyacinthacine A2 (15). Although, beta-l-homofuconojirimycin (3) and alpha-7-deoxyhomonojirimycin (alpha-7-deoxy-HNJ, 4) are previously known alkaloids, this is the first report of their occurrence in the plant family Hyacinthaceae. Alkaloid 11 was found to be a good inhibitor of bacterial beta-glucosidase and human placenta alpha-l-fucosidase, with IC50 values of 13 and 17 microM, respectively, while alkaloid 12 showed no inhibitory activity toward alpha-l-fucosidase but was a more potent inhibitor of bovine liver beta-galactosidase (IC50 = 52 microM) than 11. Alkaloids 13 and 14 were shown to be inhibitory toward mammalian alpha-glucosidase (IC50 = 45 and 77 microM, respectively), and alkaloid 14 was demonstrated as a moderate inhibitor of bacterial beta-glucosidase (IC50 = 48 microM).

Total synthesis of the proposed structures of hyacinthacines C2, C3, and their C5-epimers

“…It should be noted that the spectroscopic data of the synthetic 1a were fully consistent with those of the natural sample. 3,8 Moreover, optical rotation of the synthetic 1a (½a 25 D +12.8, H 2 O, c 0.2) also completely agreed with that of the natural sample ([a] D +12.9, H 2 O, c 0.2), confirming the absolute configuration as drawn in Figure 1.…”

“…2 Recently, Asano and co-workers have isolated new hyacinthacines C 2 (1a) and C 3 (2a) from Scilla socialis, which inhibit bacterial b-glucosidase as well as bovine liver b-galactosidase. 3 Both compounds consist of the highly oxygenated pyrrolizidine ring, whose oxygenated patterns have never been found in the other series of hyacinthacines. Specifically, no reports have appeared previously describing synthesis of these compounds.…”

Isolation and characterization of homoisoflavonoids from Scilla persica HAUSSKN

“…According to phytochemical studies performed on the Scilla species, the chemical compounds reported contain alkaloids, cardiac glycosides, stilbenes Kato et al, 2007;Nishida et al, 2008;Ono et al, 2013;Silayo, Ngadjui, Abegaz, 1999) and specially homoisoflavanones Famuyiwa et al, 2012;Ghoran et al, 2014;Heller, Tamm, 1981;Kouno, Komori, Kawasaki, 1973;Shim et al, 2004). Homoisoflavonoids were reported to be responsible for the biomedical activities of these plants, such as antibacterial, antifungal, antiallergic, antioxidant, cytotoxic and anti-angiogenic activities.…”

Enantiodivergent strategy for the synthesis of polyhydroxylated pyrrolizidines and evaluation of their inhibitory activities against glycosidases

“…More recently, we have isolated hyacinthacines A 4 , A 5 , A 6 , A 7 , B 3 , B 4 , B 5 , and B 6 from Scilla siberica bulbs, 3 hyacinthacines A 3 , A 5 , B 3 , B 4 , B 7 , C 2 , C 3 , C 4 , and C 5 from Scilla socialis bulbs. 4 These plants are also known to produce hyacinthacine derivatives bearing a long side chain at C-5. 5 The distribution of these hyacinthacines appears to be restricted to the Hyacinthaceae family examined to date and the genera Scilla is especially rich sources of them.…”