Synthesis and biological evaluation of deoxy salacinols, the role of polar substituents in the side chain on the alpha-glucosidase inhibitory activity.
Three analogs (5, 6, and 7) lacking polar substituents in the side chain of a naturally occurring alpha-glucosidase inhibitor, salacinol (1a), were synthesized by the coupling reaction of a thiosugar, 1,4-dideoxy-1,4-epithio-D-arabinitol (3), with cyclic sulfates (8, 9, and 10), and their alpha-glucosidase inhibitory activities were examined. All these simpler analogs (5, 6, and 7) showed less inhibitory activity compared to 1a, and proved the importance of cooperative role of the polar substituents for the alpha-glucosidase inhibitory activity. A practical synthetic route to 3 starting from D-xylose is also described.
Muraoka
Osamu
O
School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. muraokai@phar.kindai.ac.jp
Yoshikai
Kazuya
K
Takahashi
Hideo
H
Minematsu
Toshie
T
Lu
Guangxin
G
Tanabe
Genzoh
G
Wang
Tao
T
Matsuda
Hisashi
H
Yoshikawa
Masayuki
M
D000818:Animals; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D013058:Mass Spectrometry; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology; D013055:Spectrophotometry, Infrared; D013402:Sugar Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol