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

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Synthesis of Heterocycles in Contemporary Medicinal Chemistry

Part of the book series: Topics in Heterocyclic Chemistry ((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.

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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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Author information

Authors and Affiliations

  1. API Small Molecule Development, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium

    Sébastien Lemaire

  2. Galapagos NV, CMC Development, Gen. De Wittelaan L11 A3, 2800, Mechelen, Belgium

    Didier Schils

Authors
  1. Sébastien Lemaire
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  2. Didier Schils
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Corresponding author

Correspondence to Sébastien Lemaire .

Editor information

Editors and Affiliations

  1. Head Prototype Analytics, Sandoz Development Center Slovenia, Lek Pharmaceuticals d.d., Ljubljana, Slovenia

    Zdenko Časar

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Lemaire, S., Schils, D. (2015). Development of Efficient Routes to Access C-Glycosides as SGLT-2 Inhibitors for the Treatment of Type 2 Diabetes. In: Časar, Z. (eds) Synthesis of Heterocycles in Contemporary Medicinal Chemistry. Topics in Heterocyclic Chemistry, vol 44. Springer, Cham. https://doi.org/10.1007/7081_2015_166

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