Atom-Efficient Synthesis of Trimethine Cyanines Using Formaldehyde as a Single-Carbon Source.

Herein, we present an innovative and atom-efficient synthesis of trimethine cyanines (Cy3) using formaldehyde (FA) as a single-carbon reagent. The widespread application of Cy3 dyes in bioimaging and genomics/proteomics is often limited by synthetic routes plagued by low atom economy and substantial side-product formation. Through systematic investigation, we have developed a practical and efficient synthetic pathway for both symmetrical and unsymmetrical Cy3 derivatives, significantly minimizing resource utilization.