Uses
1,4:3,6-Dianhydro-D-mannitol is a reagent used in the synthesis of new isomannide-based peptidomimetic as human tissue kallikrein 1 inhibitor using Ugi multicomponent reaction. It also functions as a chiral ligand for stereoselective synthesis.
Synthesis
The general procedure for the synthesis of 1,4:3,6-bis-anhydromannitol from D-mannitol was as follows: 1350 g of crystalline D-mannitol was added to a reduced-pressure reactor equipped with a stirrer and heated to 170 °C to melt it. Subsequently, 10 g of 98% concentrated sulfuric acid was added to the melt, and the reaction lasted for 20 h at 170 °C and 2 kPa with nitrogen gas being passed at a flow rate of 200 mL/min. Upon completion of the reaction, the product was cooled to 90 °C and 30 g of 48% (w/w) aqueous sodium hydroxide solution was added to give crude 1,4:3,6-bis-anhydromannitol. Next, 39 g of horseshoe-based wood activated carbon (trade name: Tyco K, produced by Futamura Chemical Co., Ltd.) was added to the crude product and stirred for 3 h for decolorization to obtain a mixture to be distilled. Water was distilled from the mixture at 120 °C and 5 kPa. Subsequently, a reduced pressure distillation was carried out at 170 °C and 0.3 kPa under reduced pressure by passing nitrogen at a flow rate of 200 mL/min, resulting in 491 g of product. A portion of the distilled product was taken and the pH of the mixture was determined to be 10 according to the method of Example 1.
References
[1] Green Chemistry, 2015, vol. 17, # 2, p. A1176 - A1185
[2] Journal of Chemical Crystallography, 1997, vol. 27, # 3, p. 161 - 166
[3] Carbohydrate Research, 1980, vol. 79, p. 133 - 141
[4] Journal of Organometallic Chemistry, 1983, vol. 253, # 2, p. 249 - 252
[5] Journal of the American Chemical Society, 1946, vol. 68, p. 930,934
