Flow Photocleavage for Automated Glycan Assembly (AGA)

Abstract

Automated glycan assembly (AGA) is contingent on the development of simple, efficient cleavage strategies to liberate complex, high value products from a solid support resin. Given the rapid advances in the structural complexity of carbohydrates that can be constructed via this enabling technology, effective cleavage is a persistent challenge. Photolabile linkers have a venerable history in AGA and mitigate potential complications arising from chemically induced release protocols. However, photochemical cleavage strategies have traditionally relied upon mercury vapor lamps, which present challenges in establishing well-defined, reproducible, and nonhazardous conditions for this ultimate step of the AGA sequence. To complement the existing batch strategies, a safe and sustainable approach for the continuous flow photocleavage from solid support using LEDs has been developed. By employing a custom-built LED flow reactor, photocleavage yields of up to 80% were achieved in less than 1 h. Efficiency could be further improved by merging flow photochemistry with pregrinding. Validation of this strategy is showcased in a proof of concept AGA synthesis of a model dimannoside.