ABSTRACT
<p><b>AIM</b>To investigate more efficient synthetic method of the nitrogen analogue 4 of salacinol (1) for searching new antidiabetic agents.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>A nitrogen analogue 4 of salacinol (1) was synthesized by the coupling reaction between the cyclic sulfate 2a and an azasugar 3b.</p><p><b>CONCLUSION</b>Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably.</p>
Subject(s)
Animals , Rats , Enzyme Inhibitors , Chemistry , Pharmacology , Glycoside Hydrolase Inhibitors , Intestinal Mucosa , Molecular Structure , Nitrogen Compounds , Pharmacology , Structure-Activity Relationship , Sugar Alcohols , Chemistry , Pharmacology , Sulfates , Chemistry , Pharmacology , alpha-Glucosidases , MetabolismABSTRACT
To investigate a key strategy of the total synthesis of salacinol. Methods: A simplified analogue of salacinol (1),1-(3-sulfooxypropyl)tetrahydrothiophenium inner salt (2) was designed and synthesized by a coupling reaction between tetrahydrothiophene (THT) and 3-iodopropanol (3-IPA) followed by the esterification of the resulting sulfonium with sulfur trioxide pyridine complex (SO3*Py). Replacement of the alkylating reagent (3-IPA) of THT led to the predominate formation of a undesirable cyclic compound,2,2-dioxo-1,3,2-dioxathiane (7). Resutls:This model experiments indicated that the tandem synthetic process leading to the sulfonium sulfate 2 could be applied for the total synthesis of salacinol (1) as an alternative method.
ABSTRACT
Aim 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 Dglucose 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 α-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. Conclusion Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably.