Polyhydroxylated pyrrolidine and pyrrolizidine alkaloids from Hyancinthoides non-scripta and Scilla campanulata.
Aqueous ethanol extracts from the immature fruits and stalks of bluebell (Hyacinthoides non-scripta) were subjected to various ion-exchange column chromatographic steps to give 1,4-dideoxy-1,4-imino-D-arabinitol (1),2(R),5(R)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (2), 6-deoxy-6-C-(2,5-dihydroxyhexyl)-DMDP (3),2,5-dideoxy-2,5-imino-DL-glycero-D-manno-heptitol (homoDMDP)(4),homoDMDP-7-O-apioside (5), homoDMDP-7-O-beta-D-xylopyranoside (6), (1S*,2R*,3R*,5R*,7aR*)-1,2-dihydroxy-3,5- dihydroxymethylpyrrolizidine (7), and (1S*,2R*,3R*,5R*,6R*,7R*,7aR*)-3-hydroxymethyl-5-methyl-1,2,6,7 tetrahydroxypyrrolizidine (8). Bulbs of Scilla campanulata (Hyacinthaceae) yielded (1S*,2R*,3R*,5S*,7aR*)-1,2-dihydroxy-3,5-dihydroxy-methylpyrrol izidine (9) in addition to compounds 1-7. Compounds 3,6,7,8, and 9 are new natural products. Compound 4 is a potent competitive inhibitor with K(i) values of 1.5 microM for Caldocellum saccharolyticum beta-glucosidase and 2.2 microM for bovine liver beta-galactosidase. The 7-O-beta-D xyloside 6 was a stronger competitive inhibitor than 4 of C saccharolyticum beta-glucosidase and rat intestinal lactase, with K(i) values of 0.06 and 0.07 microM, respectively, but a weaker inhibitor of bovine liver beta-galactosidase. Furthermore, compound 4 is also a competitive inhibitor (K(i) = 1.8 microM) of porcine kidney trehalase, but 6 was inactive against this enzyme.
Kato
A
A
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Japan.
Adachi
I
I
Miyauchi
M
M
Ikeda
K
K
Komae
T
T
Kizu
H
H
Kameda
Y
Y
Watson
A A
AA
Nash
R J
RJ
Wormald
M R
MR
Fleet
G W
GW
Asano
N
N
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002852:Chromatography, Ion Exchange; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D065089:Glycoside Hydrolase Inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D043322:Lactase; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018547:Plant Stems / Q000737:chemistry; D010947:Plants, Toxic / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry / Q000302:isolation & purification; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000201:enzymology; D013552:Swine; D014198:Trehalase / Q000037:antagonists & inhibitors; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors
D000470:Alkaloids; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D006026:Glycoside Hydrolases; D043322:Lactase; D001616:beta-Galactosidase; D014198:Trehalase