Enantioselective Enzymatic Naphthoyl Ring Reduction.

Area of Science:

• Biocatalysis and enzyme mechanisms
• Organic chemistry and reaction pathways
• Spectroscopic analysis and stereochemistry

Background:

• Traditional Birch reductions of aromatic hydrocarbons require harsh conditions (alkali metals, ammonia, low temperatures).
• Enzymes like 2-naphthoyl-coenzyme A (2-NCoA) and 5,6-dihydro-2-NCoA (5,6-DHNCoA) reductases perform similar reductions under mild, ambient conditions.
• These enzymatic pathways offer potential for novel synthetic routes to complex molecules.

Purpose of the Study:

• To investigate the reaction mechanisms of 2-NCoA and 5,6-DHNCoA reductases.
• To explore the stereoselectivity of these enzymatic reductions.
• To demonstrate the utility of vibrational circular dichroism (VCD) spectroscopy in analyzing enzymatic reactions and determining stereochemistry.

Main Methods:

• Enzymatic reduction assays using substrate analogues.
• Mechanistic studies involving intermediate identification (Meisenheimer complex-analogous intermediate).
• Vibrational circular dichroism (VCD) spectroscopy in D2O to analyze stereoselectivity and absolute configuration.

Main Results:

• Evidence for a Meisenheimer complex-analogous intermediate in 2-NCoA reduction.
• Suggestion of a cationic transition state in the subsequent reduction of 5,6-DHNCoA.
• High stereoselectivity observed in both enzymatic reductions, yielding enantioselective pathways.
• Demonstration of VCD spectroscopy's capability to determine absolute configurations of stereocenters.

Conclusions:

• Enzymatic reductions of NCoA provide a mild and highly stereoselective alternative to chemical methods.
• The identified intermediates and transition states offer insights into enzyme mechanisms.
• VCD spectroscopy is a powerful tool for characterizing stereoselective enzymatic transformations and determining absolute configurations.