1,3-Dithiolane as a Privileged Scaffold in Bioactive Derivatives: Chiral Resolution and Assignment of Absolute...

Area of Science:

• Medicinal Chemistry
• Organic Chemistry
• Stereochemistry

Background:

• The 1,3-dithiolane ring is a valuable scaffold in drug design.
• Chiral resolution is crucial for derivatives substituted at position 4, introducing a stereocenter.
• Existing methods for chiral dithiolane synthesis and characterization are limited.

Purpose of the Study:

• To report the first chiral resolution and absolute configuration (AC) assignment for (1,4-dithiaspiro[4.5]decan-2-yl)methanol (R/S)-1.
• To establish a reliable method for preparing enantiopure 1,3-dithiolane scaffolds.
• To provide reference standards for AC determination of related compounds.

Main Methods:

• (Semi)preparative enantioselective High-Performance Liquid Chromatography (HPLC) for isolating enantiomers.
• Enantioselective synthesis utilizing the resolved chiral synthon.
• X-ray diffraction analysis for absolute configuration determination.

Main Results:

• Successful chiral resolution and AC assignment of (1,4-dithiaspiro[4.5]decan-2-yl)methanol (1).
• Isolation of enantiomeric forms of compound 1 using enantioselective HPLC.
• Confirmation of the (R)-configuration of (+)-1 through synthesis and X-ray analysis of a sigma receptor modulator (+)-BS148.

Conclusions:

• A reliable method for preparing enantiopure 1,3-dithiolane scaffolds has been established.
• The reported approach provides essential reference standards for AC determination in related compounds.
• This work advances the utility of dithiolane scaffolds in drug design and development.