2,3,4,6-Tetrakis-O-Trimethylsilyl-D-Gluconolactone

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)-glChemicalbookuconicaciddelta-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;
(3R,5R,6R)-3,4,5-Tris((trimethylsilyl)oxy)-6-(((trimethylsilyl)oxy)methyl)
tetrahydro-2H-pyran-2-one

CAS number

32384-65-9

Molecular formula

C18H42O6Si4

Molecular weight

466.87

EINECS number

608-732-8

Boiling point

417℃

Density

0.97

Flash point

171℃

Storage conditions

under inert gas (nitrogen or Argon) at 2-8℃

Solubility

Chloroform (slightly soluble), ethyl acetate (slightly soluble), methanol (slightly soluble)

Form

Oily

Color

Colorless to pale yellow

Optical rotation

46.568°(C=0.01g/ml CHCL3)

Stability

Moisture sensitive

InChl

InChl=1/C18H4206Si4/c1-25(2,3)20-13-14-15(22-26(4,5)6)16(23-27(7,8)9)17
(18(19)21-14)24-28(10,11)12/ h14-17H,13H2,1-12H3/t14-,15-,16+,17-/s3

InChlKey

VNGTZLYNGGLPIZ-NELUYGJANA-N

SMILES

O([C@@H]1[C@H](C(=O)O[C@H](CO[Si](C)(C)C[C@H]10[Si](C)(C)CO[Si](C)(C)C[Si](C)(C)C|&1:1,2,6,13,r|

Overview

Canagliflozin (1) is chemically named (1S)-1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol.
It was jointly developed by Mitsubishi Tanabe and Johnson & Johnson and was approved by the US FDA for marketing 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 reabsorbed
smoothly into the blood and being excreted in the urine, thereby reducing blood glucose concentration.

Uses

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-Chemicalbook tetra-O-trimethylsilyl-D-glucosyl-1,5-lactone is used as a reagent for synthesizing C-glucose containing
trans-cyclohexane 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 symptoms such as reproductive system infection, polyuria and frequent urination 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

Using gluconolactone (2) as the starting material, it reacts with trimethylsilyl chloride in tetrahydrofuran under the catalysis of
N-methylmorpholine (NMM) 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) is treated with n-butyl lithium at -8°C and condensed with compound
3 to obtain compound 5 (the condensation reaction temperature is controlled at -Chemic albook7～0℃); after the reaction,
the reaction temperature is maintained,and the reaction solution is not treated, and methanesulfonic acid and methanol are added dropwise thereto,
and the temperature is slowly raised to room temperature and stirred to obtain deprotected compound 6 (the yield of this step is 91.3%,
and the product purity is 88.5%);Compound 6 is reduced with triethylsilane (Et3SiH) or triisopropylsilane (TIPS) and boron
trifluoride etherate to obtain canagliflozin (1),and the yield of this step is 56.7%, and the product purity is 99.5%.

Upstream raw materials

Hexamethyldisilazane, trimethylchlorosilane, gluconolactone, N-methylmorpholine, tetrahydrofuran, 4-dimethylaminopyridine (DMAP)