The Breaking Beads Approach for Photocleavage from Solid Support

Abstract

Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. The photocleavage, usually performed by batch irradiation, suffers from incomplete and slow cleavage. To overcome these issues, continuous flow and high-energy lamps are frequently used, but these setups are hazardous, technically challenging, and expensive. We developed a photocleavage approach that relies on a benchtop LED lamp and magnetic stirring. In this approach, we crush the beads instead of keeping their integrity to increase the yield of photocleavage. This approach proved very efficient for photocleavage of protected oligosaccharides.

Recent Developments in Solid-Phase Glycan Synthesis

“…These linkers are normally cleaved with UV light (366 nm), facilitated by the implementation of a continuous flow system and high-power mercury lamps. 39 However, the formation of side products absorbing UV light, 102 together with the inefficient penetration of light into the pores of the solid support, 103 result in photocleavage yields of about 60–70%. 38 Grinding the beads with magnetic stirring prior to or during irradiation was suggested to improve the photocleavage process.…”

“…The exposure of more resin surface to light allowed the photocleavage step to be performed efficiently with a simple light-emitting diode (LED) batch system. 103 So far, this approach has proven successful only for a disaccharide, which was isolated in 80% yield after 6 hours of irradiation time. Promising results were also obtained with a LED-based flow photocleavage platform.…”