Synthesis of a salacinol analogue and its alpha-glucosidase inhibitory activity.
OBJECTIVE
To investigate more efficient synthetic method of the nitrogen analogue 4 of salacinol (1) for searching new antidiabetic agents.


METHODS
The synthesis of the key intermediate 2, 4-O-isopropylidene-L-erythritol 1,3-cyclic sulfate (2a) was accomplished by modification of reports from D-glucose via seven steps in much more less expensive. Using this method, an efficient synthesis of 4 was carried out. The glycosidase inhibitory activity of 4 was tested for the intestinal alpha-glucosidase in vitro and compared with that of salacinol.


RESULTS
A nitrogen analogue 4 of salacinol (1) was synthesized by the coupling reaction between the cyclic sulfate 2a and an azasugar 3b.


CONCLUSIONS
Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably.
Shao
Ying
Y
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. shaoy@cde.org.cn
Osamu
Muraoka
M
Kazuya
Yoshikai
Y
Yoshiharu
Matsuura
M
Eriko
Yamada
Y
Toshie
Minematsu
M
Genzoh
Tanabe
T
Hisashi
Matsuda
M
Masayuki
Yoshikawa
Y
You
Qi-dong
QD
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D017672:Nitrogen Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017672:Nitrogen Compounds; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol; D000520:alpha-Glucosidases