The unnatural, alkyne-containing nucleoside analog islatravir
(MK-8591) is synthetically accessed through a biocatalytic cascade starting from
2-ethynylglycerol as a building block. Herein, we describe the development of an
efficient synthesis of this building block including the initial route, route
scouting and final process development. Key challenges that have been overcome are
the development of an efficient and safe acetylenic nucleophile addition to an appropriate
ketone, and the identification of a 2-ethynylpropane-1,2,3-triol derivative
with favorable physical properties. An acid-catalyzed cracking of commercially
available 1,3-dihydroxyacetone dimer and subsequent 1,2-addition of an
acetylenic nucleophile has been discovered and optimized into the manufacturing
process
Manufacturing Process Development For Polymer-based Microfluidics Device
