Biocatalytic Aldol Addition of Simple Aliphatic Nucleophiles to Hydroxyaldehydes

Area of Science:

• Biocatalysis
• Organic Synthesis
• Enzymology

Background:

• Asymmetric aldol addition is crucial for synthesizing complex molecules like unusual sugars and chiral building blocks.
• Enzymatic aldol additions offer a stereoselective route to valuable chemical intermediates.

Purpose of the Study:

• To investigate engineered d-fructose-6-phosphate aldolase (FSA) D6X variants as catalysts.
• To explore the aldol addition of simple aldehydes and ketones to hydroxyaldehydes using these variants.

Main Methods:

• Utilized engineered FSA D6H and D6Q variants as biocatalysts.
• Performed aldol additions with nucleophiles like propanone, cyclobutanone, cyclopentanone, or ethanal.
• Reacted nucleophiles with hydroxyaldehyde substrates such as 3-hydroxypropanal or (S)-/ (R)-3-hydroxybutanal.

Main Results:

• Synthesized rare deoxysugars with isolated yields ranging from 8% to 77%.
• Achieved high stereoselectivity in the aldol addition products, with diastereomeric ratios (dr) of 97:3 and enantiomeric excess (ee) greater than 95%.

Conclusions:

• Engineered FSA D6X variants are effective catalysts for asymmetric aldol additions.
• This biocatalytic approach provides a stereoselective method for producing valuable deoxysugars and chiral synthons.