(200o) Liquid Phase Synthesis of Monodisperse PEGs By Nanostar Sieving
AIChE Annual Meeting
Monday, October 29, 2018 - 3:30pm to 5:00pm
We have developed a scalable synthetic platform for the manufacture of sequence-defined heteropolymers and monodisperse homopolymers â Nanostar Sieving technology â that combines liquid phase coupling reactions with purification through a size-selective polymer membrane. Three strands of polymer are grown unidirectionally from a central hub giving a polymer nanostar. A rigid central hub was developed that both maximises membrane rejection of the growing polymer-star and provides a distinct chromatographic marker (lambda max = 290 nm).
This approach has been applied to oligonucleotides [Gaffney et al. Chem. Eur. J. 2015, 21, 9535-43] and peptides, but is even more appropriate to polyethers. Solid phase methods and supports are poorly compatible with Williamson etherification. By contrast, solution phase chain extension of PEG-stars is unaffected by mass transfer kinetics, the hub is chemically inert, and slow reactions (hours) can be continuously monitored to completion. PEG-star chain elongation was explored using Thp or Dmtr protected dodecagol (Eg12) toluene sulfonate building blocks, up to mono-methyl Eg60 (mPEG-2675) and Eg112 (PEG-4951), respectively. Synthesis of and purification of monodisperse PEG by nanostar sieving is ideal for efficient heterobifunctionalisation of the chain termini [Livingston et al. Chem. Eur. J. 2014, 20, 10038-51], and new building blocks are being developed to permit intra-chain functionalization at precise positions along the sequence.
This technology is being commercialised by EXACTMER, a new start-up from Imperial College London.