Development Of Alternative BCDP Reagents For The Synthesis Of 5' -Terminal Phosphate Oligonucleotides: Application In The Synthesis Of SmartCap, A Novel mRNA Capping Reagent

BCDP (Bis(2-cyanoethyl) diisopropylphosphoramidite) is a phosphitylating agent crucial for forming phosphite triester bonds in oligonucleotide synthesis, which are then used to produce terminal phosphate or thiophosphate building blocks. However, BCDP is challenging to handle due to concerns related to its stability, exothermicity, and toxicity; it's classified as a flammable liquid and vapor, an UN class 1 explosive candidate, and exhibits significant purity loss at room temperature.

To address these safety concerns, alternative phosphitylating reagents were developed and analyzed using Accelerating Rate Calorimetry (ARC) and Differential Scanning Calorimetry (DSC). These analyses confirmed that the alternative reagents exhibit reduced hazardous characteristics compared to BCDP. Furthermore, the study demonstrated that these substitutes effectively replace BCDP in the synthesis of dinucleotides required for SmartCap®—a novel mRNA capping reagent—achieving equivalent or higher yields. Dive into the poster to see the detailed thermal stability comparisons and application data for these safer phosphoramidite alternatives.