English Synonyms
(3R,4S,5R,6R)-3,4,5-tris(triMethylsilyloxy)-6-((triMethylsilyloxy)Methyl)tetrahydro-2H-pyran-2-one;(3R,4S,5R,6R)-3,4,5-Tris[(trimethylsilyl)oxy]-6-[[(trimethylsilyl)oxy]methyl]tetrahydropyran-2-one;2,3,4,6-Tetrakis-O-trimethylsilyl-D-gluconolactone;D-2,3,4,6-Tetrakis-O-(trimethylsilyl)-gluconicaciddelta-lactone;D-Gluconicacid,2,3,4,6-tetrakis-O-(triMethylsilyl)-,δ-lactone;2,3,4,6-Tetrakis-O-triMethylsilyl-D-gluconolactoe;D-Gluconicacid,2,3,4,6-tetrakis-O-(triMethylsilyl)-,d-lactone;2,3,4,6-tetrakis-O-trimethylsilyl-D-glucono1,5lactone
2,3,4,6-Tetrakis-O-Trimethylsilyl-D-Gluconolactone Properties
| Boiling Point | 417℃
|
| Density | 0.97 |
| Flash Point | 171℃ |
| Storage Condition | Under Inert Gas (Nitrogen or Argon) at 2-8°c |
| Solubility | Chloroform (Slightly Soluble), Ethyl Acetate (Slightly Soluble), Methanol (Slightly Soluble) |
| Form | Oily |
| Color | Colorless to Light Yellow |
| Stability | Moisture Sensitive |
Usage and Synthesis of 2,3,4,6-Tetrakis-O-Trimethylsilyl-D-Gluconolactone
Overview
Canagliflozin (1), With the Chemical Name (1s)-1,5-Anhydro-1-C-[3-[[5-(4-Fluorophenyl)-2-Thienyl]methyl]-4-Methylphenyl]-D-Glucitol, Was Jointly Developed by Mitsubishi Tanabe Corporation and Johnson & Johnson. It Was Approved for Marketing by the Us Fda on March 29, 2013. It Is the First Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor Approved by the Fda. The Drug Was Approved by the European Commission (Ec) on November 25, 2013 for the Treatment of Type 2 Diabetes in Adults. Canagliflozin Inhibits Sglt2, Preventing Glucose in the Renal Tubules from Being Smoothly Reabsorbed into the Blood and Excreted in the Urine, Thereby Reducing Blood Sugar Concentration.
Use
2,3,4,6-Tetra-O-Trimethylsilyl-D-Glucosyl-1,5-Lactone Is an Antidiabetic Drug and an Intermediate of Dapagliflozin. 2,3,4,6-Tetra-O-Trimethylsilyl-D-Glucosyl-1,5-Lactone Is Used as a Reagent for the Synthesis of Trans-Cyclohexane-Containing C-Glucose and as a Sodium-Glucose Cotransporter 2 Inhibitor.
Clinical Application
Canagliflozin Can Reduce Patients; Fasting Blood Sugar, Glycosylated Hemoglobin and Body Weight, And the Use of This Drug Can Significantly Reduce the Risk of Hypoglycemia During Treatment. Although the Incidence of Reproductive System Infection, Polyuria, Frequent Urination and Other Symptoms Is Still Relatively High Compared with the Control Group, It Still Has a Very Obvious Effect in Lowering Blood Sugar. It Has Important Clinical Significance and Value in the Treatment of Clinical Type 2 Diabetes.
Preparation
Gluconolactone (2) Was Used as the Starting Material. Under the Catalysis of N-Methylmorpholine (Nmm), It Reacted with Trimethylsilyl Chloride in Tetrahydrofuran to Obtain the Key Intermediate 2,3,4,6-Tetra-O-Trimethylsilyl-D-Gluconolactone (3). 2-[(5-Bromo-2-Methylphenyl)methyl]-5-(4-Fluorophenyl)thiophene (4) Was Treated with N-Butyl Lithium at -8 °c and Then Condensed with Compound 3 to Obtain Compound 5 (The Condensation Reaction Temperature Was Controlled at -7 to 0 °c). After the Reaction, The Reaction Temperature Was Maintained and the Reaction Solution Was Not Treated. Methanesulfonic Acid and Methanol Were Added Dropwise Thereto. The Temperature Was Slowly Raised to Room Temperature and Stirred to Obtain the Deprotected Compound 6 (The Yield of This Step Was 91.3% and the Product Purity Was 88.5%). Compound 6 Was Treated with Triethylsilane (Et3sih) or Triisopropylsilane (Tips). 5%。 and Boron Trifluoride Ether Reduction to Give Canagliflozin (1), The Step Yield Was 56.7%, The Product Purity Was 99.
