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.

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.

AIMTo investigate more efficient synthetic method of the nitrogen analogue 4 of salacinol (1) for searching new antidiabetic agents.

METHODSThe 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.

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

CONCLUSIONSubstitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably.

Animals ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Glycoside Hydrolase Inhibitors ; Intestinal Mucosa ; drug effects ; enzymology ; Molecular Structure ; Nitrogen Compounds ; chemical synthesis ; pharmacology ; Rats ; Structure-Activity Relationship ; Sugar Alcohols ; chemical synthesis ; chemistry ; pharmacology ; Sulfates ; chemical synthesis ; chemistry ; pharmacology ; alpha-Glucosidases ; metabolism

Neokotalanol, a potent α-glucosidase inhibitor isolated from Salacia reticulata, was synthesized through a key coupling reaction between a perbenzylated thiosugar and an appropriately protected perseitol triflate derived from D-mannose. This key step was found to be quite temperature dependent, and a simultaneous cyclization of the triflate leading to a characteristic 2,4,7-trioxabicyclo[4.2.1]nonane system was detected.
Enzyme Inhibitors ; chemical synthesis ; chemistry ; Glycoside Hydrolase Inhibitors ; Plant Extracts ; chemical synthesis ; chemistry ; Salacia ; chemistry

A 36-year-old man underwent direct closure of an atrial septal defect through median sternotomy at the age of 14. He also underwent a mitral valve replacement with tricuspid annuloplasty using the same approach at the age of 18. The patient also presented with pretibial edema and congestive liver disease at the age of 27 and the pretibial edema progressed at the age of 35. Hypoalbuminemia (TP ; 3.6 g/dl, Alb ; 1.6 g/dl) was also observed. Further examinations were performed, which revealed that the right ventricular pressure curve presented a dip and plateau pattern by cardiac catheterization. Computed tomography of the chest additionally revealed thickened and calcified pericardium in the left ventricle. Abdominal scintigraphy showed tracer accumulation in the transverse colon hepatic flexure 4 h after intravenous administration of technetium-99m-labelled human serum albumin. The patient was diagnosed with a protein-losing gastroenteropathy caused by constrictive pericarditis. He underwent pericardiectomy via left anterior thoracotomy without cardiopulmonary bypass. No complications were present after the surgery, and he was discharged after 46 postoperative days. Following his discharge from the hospital, the pretibial edema disappeared, and serum albumin levels gradually increased and normalized within 3 months after the surgery (TP 7.1 g/dl, Alb 4.2 g/dl).