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Development of Efficient Routes to Access C-Glycosides as SGLT-2 Inhibitors for the Treatment of Type 2 Diabetes

Chapter
Part of the Topics in Heterocyclic Chemistry book series (TOPICS, volume 44)

Abstract

C-Glycosides represent an attractive class of compounds for the medicinal chemist because they are more resistant to enzymatic hydrolysis than O-glycosides and therefore are considered as potential drug candidates. The potential was confirmed by the emergence of a new family of C-glycosides known as the SGLT-2 inhibitors leading to the development of new drugs for the treatment of type 2 diabetes. In this chapter, chemical processes to access new active pharmaceutical ingredients (API) will be described focusing on the key C-glycosylation step.

Keywords

C-glycosylation Canagliflozin Dapagliflozin Ertugliflozin Ipragliflozin Luseogliflozin Sotagliflozin Tofogliflozin 

Abbreviations

Ac

Acetyl

acac

Acetylacetonate

API

Active pharmaceutical ingredient

Ar

Aryl

Bn

Benzyl

Bz

Benzoyl

d

Day(s)

DBE

Di-n-butyl ether

DIBAL-H

Diisobutylaluminum hydride

DMAP

4-(Dimethylamino)pyridine

DMP

Dess–Martin periodinane

DMSO

Dimethyl sulfoxide

equiv

Equivalent(s)

Et

Ethyl

Et3SiH

Triethylsilane

h

Hour(s)

i-Pr

Isopropyl

LG

Leaving group

L-PGA

l-Pyroglutamic acid

Me

Methyl

MSA

Methanesulfonic acid

MTBE

Methyl tert-butyl ether

n-Bu

Butyl

n-Hex

n-Hexane

Nu

Nucleophile

PG

Protecting group

Ph

Phenyl

Piv

Pivaloyl

PMB

4-Methoxyphenyl

PNB

4-Nitrobenzoyl

py

Pyridine

R

Alkyl

rt

Room temperature

s-Bu

sec-Butyl

TBAF

Tetrabutylammonium fluoride

TBDPS

tert-Butyldiphenylsilyl

t-Bu

tert-Butyl

TEA

Triethylamine

TFA

Trifluoroacetic acid

THF

Tetrahydrofuran

TMEDA

N,N,N',N'-Tetramethyl-1,2-ethylenediamine

TMS

Trimethylsilyl

Tol

Toluene, 4-methylphenyl

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.API Small Molecule Development, Janssen Research and DevelopmentBeerseBelgium
  2. 2.Galapagos NV, CMC DevelopmentMechelenBelgium

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