Merck/Codexis Magic: Biocatalytic Synthesis of Islatravir
By Michael Lambrecht We all knew process scientists were good, but the Merck and Codexis teams just took it to another level! Unnatural nucleosides like Merck’s reverse transcriptase inhibitor islatravir (1, Figure 1) are well-known to be challenging to synthesize by traditional methods, as evidenced by several published chemical syntheses of this molecule requiring a…
Adventures in Atropisomerism: A Case Study from BMS
BMS-986142 is a reversible BTK inhibitor with two axial stereocenters. BMS synthetic chemists were able to make >200 kilos of this compound as a single isomer using this route. Wow. Atropisomers are a nightmare in drug discovery. Axial stereocenters are not easy to set predictably, separation of isomers is a pain, and the products are…