A model reaction for assessing the coupling and chiral efficiency of reagents in depside bond formation

Abstract

The formation of Fmoc-L-Ala-L-Phlac-OBzl (and Fmoc-D-AIa-L-Phlac-OBzl if there is racemisation) has been monitored by HPLC analysis for a number of coupling conditions between Fmoc-L-AIa-OH and H-Phlac-OBzl. For this depside link formation it is revealed that CDI, DCC/DMAP and mixed anhydride couplings gave yields near to 50%. Couplings via TBTU, TNTU and TSTU gave lower yields. The best yields were achieved by acid chloride (61%), urethane-N-carboxyanhydrides (80%) and by PyBroP coupling (82%).