Synthesis and applications of a novel tandem ring-closing metathesis cleavable linker for solid phase synthesizers

S4.3 Synthetic innovation in glycan assembly
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 11:45 to 12:00

Jacopo Enotarpi1, Jeanine van Mechelen1, Elko Peterse1, Mickey Harvey1, Hermen S. Overkleeft1, Gijs A. van der Marel1, Jeroen Codée1

1Leiden University, Leiden, The Netherlands

Since the early 1960s, when R. Merrifield first introduced the term “solid phase synthesis”, researchers have focused their efforts on establishing new methods and machines to streamline the synthesis of oligomers (peptides, oligonucleotides and oligosaccharides).[1] The linker —used to connect the first synthon to the solid support—plays a key role in solid phase synthesis; the ideal linker system is stable towards all elongation cycle and deprotection conditions and is efficiently cleaved from the solid support at the end of the synthesis under conditions that do not affect the remaining functionalities of the oligomer. To this end, we present in this work a novel tandem Ring-Closing Metathesis (RCM) linker and its applications in biologically relevant oligomer production, such as E. faecalis diheteroglycan oligosaccharides, bacterial β-(1,3)-glucans and bacterial teichoic acid fragments (fig. 1) utilizing automated solid-phase synthesizers. This new RCM-linker is easily synthesized, stable under acidic and basic media, and no additives are necessary during the cleavage from the polymeric support under mild and neutral conditions.[2] It delivers the target compounds -after deprotection- with a suitable amine handle for further conjugation purposes.

  1. R. B. Merrifield, J. Am. Chem. Soc., 1963, 85 (14), pp 2149–2154; Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Science 2001, 291, 1523
  2. Timmer, M. S. M.; Codée, J. D. C.; Overkleeft, H. S.; Van Boom, J. H.; van der Marel, G. A.; Synlett, 2004, 12, 2155-2158