Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition

Wai Lung Ng, Ho Chuen Li, Kit Man Lau, Anthony K.N. Chan, Clara Bik San Lau, Tony Kung Ming Shing

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of structure-activity relationship (SAR) studies of these compounds. Herein, we report a concise and stereodivergent synthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regioselective, and stereospecific palladium-catalyzed allyl-aryl coupling reaction. This synthetic strategy, together with computational modeling, revealed the unexpected SAR of these carbasugar SGLT2 inhibitors, and enabled the discovery of a highly selective and potent SGLT2 inhibitor.

Original languageEnglish
Article number5581
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

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Carbasugars
Sodium-Glucose Transport Proteins
Palladium
Medical problems
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

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Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition. / Ng, Wai Lung; Li, Ho Chuen; Lau, Kit Man; Chan, Anthony K.N.; Lau, Clara Bik San; Shing, Tony Kung Ming.

In: Scientific Reports, Vol. 7, No. 1, 5581, 01.12.2017.

Research output: Contribution to journalArticle

Ng, Wai Lung ; Li, Ho Chuen ; Lau, Kit Man ; Chan, Anthony K.N. ; Lau, Clara Bik San ; Shing, Tony Kung Ming. / Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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