Synthesis of a potent aminocyclitol alpha-mannosidase inhibitor, 1L-(1,2,3,5/4)-5-amino-4-O-methyl-1,2,3,4-cyclopentanetetrol.
Demethylthio-, de-S-methyl-, and ethylthio-derivatives of the alpha-mannosidase inhibitor, mannostatin A, have been synthesized and evaluated for their inhibition of Jack bean alpha-mannosidase in order to elucidate the roles of the methylthio group. All derivatives had lowered inhibitory potentials. However, a mannostatin A analogue with a methoxyl instead of the methylthio, exhibited about 2-fold enhancement of the activity, indicating an importance for the methyl group rather than the sulfur atom.
Ogawa
S
S
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan. ogawa@applc.keio.ac.jp
Morikawa
T
T
D001671:Biochemistry / Q000379:methods; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008361:Mannosidases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C413728:5-amino-4-O-methyl-1,2,3,4-cyclopentanetetrol; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; C060107:mannostatin A; D008361:Mannosidases; C413730:aminocyclitol alpha-mannosidase