Luseogliflozin (hydrate)
- CAS No.
- 1152425-66-5
- Chemical Name:
- Luseogliflozin (hydrate)
- Synonyms
- TS 071 hydrate;Luseogliflozin (hydrate);(2S,3R,4R,5S,6R)-2-[5-[(4-ethoxyphenyl)methyl]-2-methoxy-4-methylphenyl]-6-(hydroxymethyl)thiane-3,4,5-triol:hydrate
- CBNumber:
- CB62716277
- Molecular Formula:
- C23H32O7S
- Molecular Weight:
- 452.56
- MDL Number:
- MFCD34574461
- MOL File:
- 1152425-66-5.mol
Luseogliflozin (hydrate) Chemical Properties,Uses,Production
Description
Luseogliflozin hydrate, which is an SGLT2 inhibitor approved in Japan in March 2014 for the treatment of type 2 diabetes, was discovered by Taisho Pharmaceutical and jointly developed and marketed with Novartis as Lusefi®. Luseogliflozin selectively binds and inhibits human SGLT2 with a Ki of 1.10 nM and IC50 value of 2.26 nM.
Synthesis
The most likely synthetic route capable of producing luseogliflozin
on process scale has been reported by Taisho. Commercially available 4-methoxy-
2-methyl-benzoic acid (160) was brominated in the presence
of a catalytic amount of iron powder, generating a 1:1 mixture of
3- and 5-bromo derivatives which were separable by recrystallization
from methanol to provide the desired regioisomer 161 in 34%
yield. Next, benzoic acid 161 was treated with oxalyl chloride to
give the corresponding acyl chloride 162, which underwent a Friedel¨C
Crafts reaction with ethoxybenzene (163) to afford 164 in 82%
yield for the two step sequence. The dibenzylic ketone 164 was
reduced using triethylsilane and boron trifluoride to give aglycon
165 in 99% yield. The Grignard reagent prepared from bromide
165 was then alkylated with thiolactone 166 (prepared from 5-
thio-D-glucose penta-O-acetate (169) as illustrated in Scheme 27)
to give rise to hemithioacetal 167 in 75% yield. This compound
underwent stereoselective reduction to provide thioglycoside 168
in 77% yield. Hydrogenation of 168 resulted in global debenzylation
to provide the desired product luseogliflozin (XIX) in 81%
yield.
The preparation of key thiolactone 166 started from 5-thio-Dglucose
penta-O-acetate (169) ; 169
could be prepared by eight steps from commercially available Dglucurono-
3,6-lactone. The anomeric acetyl group of 169
was selectively removed by hydrazine and acetic acid at room temperature
giving compound 170 in 70% yield. Subsequently, the
anomeric hydroxyl group of 170 was protected with tetrahydropyran.
Then, all acetyl groups of 171 were removed by Zempl¨|n
deacetylation, and the resulting hydroxyl groups of 172 were further
protected by benzyl groups using benzylbromide with sodium
hydride to generate 173. The tetrahydropyranyl group of 173 was
removed using pyridinium p-toluenesulfonate (PPTS), followed by
DMSO oxidation to provide 166 in 82% yield, by way of 174.
Luseogliflozin (hydrate) Preparation Products And Raw materials
Raw materials
Preparation Products
Luseogliflozin (hydrate) Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Lynnchem | 86-(0)29-85992781 17792393971 | info@lynnchem.com | China | 4587 | 58 |
| Novachemistry | 44-20819178-90 02081917890 | info@novachemistry.com | United Kingdom | 4381 | 58 |
| Suzhou Haiben Pharmaceutical Co., Ltd | 14760821013 13564957716 | 1816280386@qq.com | China | 7326 | 58 |
| TargetMol Chemicals Inc. | 15002134094 | marketing@targetmol.cn | China | 19711 | 58 |
| Supplier | Advantage |
|---|---|
| Lynnchem | 58 |
| Novachemistry | 58 |
| Suzhou Haiben Pharmaceutical Co., Ltd | 58 |
| TargetMol Chemicals Inc. | 58 |