2,3,4,6-Tetrakis-O-triMethylsilyl-D-gluconolactoe

The chemical name of canagliflozin (1) is (1S)-1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]- 4-Methylphenyl]-D-glucitol, jointly developed by Mitsubishi Tanabe and Johnson & Johnson, was approved by the US FDA on March 29, 2013. It is the first sodium-glucose co-transporter 2( SGLT2) inhibitors. The drug was approved by the European Commission (EC) on November 25, 2013, for the treatment of type 2 diabetes in adults. By inhibiting SGLT2, canagliflozin prevents glucose in the renal tubules from being smoothly reabsorbed into the blood and is excreted in the urine, thereby reducing blood glucose concentration. Purpose: 2,3,4,6-Tetramethylsilyl-D-glucosyl-1,5-lactone is an anti-diabetic drug and an intermediate of dapagliflozin. 2,3,4,6-Tetrakis-O-trimethylsilyl-D-glucosyl-1,5-lactone as a reagent for the synthesis of trans-cyclohexane-containing C-glucose and as a sodium glucose cotransporter Protein 2 inhibitor. The clinical application of canagliflozin drugs can reduce patients' fasting blood glucose, glycosylated hemoglobin and body weight, and the use of this drug can significantly reduce the risk of hypoglycemia during treatment. The symptoms are still relatively high compared to the control group, but it still has a very obvious effect in lowering blood sugar. It has very important clinical significance and value in the clinical treatment of type 2 diabetes. The preparation uses gluconolactone (2) as the starting material, reacts with trimethylchlorosilane in tetrahydrofuran under the catalysis of N-methylmorpholine (NMM), and obtains the key intermediate 2,3,4,6- Tetrakis-O-trimethylsilyl-D-gluconolactone (3); 2-[(5-bromo-2-methylphenyl)methyl]-5-(4-fluorophenyl)thiophene ( 4) After treatment with n-butyllithium at -8°C, it is condensed with compound 3 to obtain compound 5 (the condensation reaction temperature is controlled at -7~0°C); after the reaction is completed, the reaction temperature is maintained, and the reaction solution is dripped into it without treatment. Add methanesulfonic acid and methanol, slowly rise to room temperature and stir to obtain deprotected compound 6 (the yield of this reaction is 91.3%, and the product purity is 88.5%); compound 6 is treated with triethylsilane (Et3SiH) or triethylsilane. Canagliflozin (1) was obtained by reduction of isopropylsilane (TIPS) and boron trifluoride ether. The yield of this step was 56.7%, and the purity of the product was 99.5%.

2,3,4,6-Tetrakis-O-trimethylsilyl-D-glucosyl-1,5-lactone is an antidiabetic drug and an intermediate of dapagliflozin. 2,3,4,6-tetraChemicalbook-O-trimethylsilyl-D-glucosyl-1,5-lactone is used as a reagent for the synthesis of trans-cyclohexane-containing C-glucose and as sodium glucose co- Transporter 2 inhibitors.