What question did this study set out to answer?

This research aims to synthesize novel 1'-homologated-3'-modified adenosine derivatives as potential PPARγ modulators.

April 10, 2026

Synthesis of 1′-Homologated-3′-Modified Adenosine Derivatives through Asymmetric Intramolecular S N 2′ Alkylation Using an Evans Chiral Auxiliary

Key Points

This research aims to synthesize novel 1'-homologated-3'-modified adenosine derivatives as potential PPARγ modulators.
Developed synthesis using Evans oxazolidinone-based methodology.
Carried out asymmetric intramolecular S<sub>N</sub>2' alkylation.
Used density functional theory calculations to analyze cis-selectivity and transition states.
Successfully synthesized 1'-homologated-3'-modified adenosine derivatives.
Achieved high stereoselectivity for cis-tetrahydrofuran through specific interactions.
Density functional theory confirmed stabilizing noncovalent interactions influencing product formation.

Abstract

1'-Homologated-3'-modified adenosine derivatives were designed and synthesized as peroxisome proliferator-activated receptor γ (PPARγ) modulators. The stereoselective synthesis of cis-tetrahydrofuran was achieved through an Evans oxazolidinone-based methodology, generating two stereogenic centers via an asymmetric intramolecular SN2' alkylation. Density functional theory calculations confirmed the reason behind the cis-selectivity, highlighting the role of noncovalent interactions between the oxazolidinone and allylic functionality that stabilize the key transition state structure leading to the major product.

Synthesis of 1′-Homologated-3′-Modified Adenosine Derivatives through Asymmetric Intramolecular S N 2′ Alkylation Using an Evans Chiral Auxiliary

Key Points

Abstract

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