Alpha-rhamnosidase inhibitory activities of polyhydroxylated pyrrolidine.
We designed and synthesized polyhydroxylated pyrrolidines 1-12 from L-tyrosine, L-phenylalanine, and D-tyrosine through iodine-mediated intramolecular cyclization followed by Woodward-Prevost reaction. The synthetic polyhydroxylated pyrrolidines were identified with structure-based inhibitory activity and selective inhibitory activity against alpha-rhamnosidase. (2S,3S,4R)-deacetyl anisomycin 7 was the best inhibitor among the 12 polyhydroxylated pyrrolidines because it possesses the same stereoconfiguration at C1, C2, C3 as alpha-L-rhamnopyranoside. An investigation into the nature of the inhibition showed that the synthetic pyrrolidines are competitive inhibitors. They also did not have remarkable inhibitory activity against seven glycosidases (alpha-glucosidase, alpha-mannosidase, alpha-amylase, beta-glucosidase, beta-galactosidase, beta-amylase, and invertase).
Kim
Jin Hyo
JH
Division of Applied Life Science (BK21 program), Department of Agricultural Chemistry, Institute of Agriculture and Life Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Curtis-Long
Marcus J
MJ
Seo
Woo Duck
WD
Lee
Jin Hwan
JH
Lee
Byong Won
BW
Yoon
Yong Jin
YJ
Kang
Kyu Young
KY
Park
Ki Hun
KH
D000596:Amino Acids / Q000737:chemistry; D000841:Anisomycin / Q000138:chemical synthesis / Q000494:pharmacology; D001667:Binding, Competitive; D003500:Cyclization; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000596:Amino Acids; D011759:Pyrrolidines; D000841:Anisomycin; D006026:Glycoside Hydrolases; C022525:alpha-L-rhamnosidase; C032519:pyrrolidine