Premium
Phosphoramitoids—A submonomer approach to sequence defined N ‐substituted phosphoramidate polymers
Author(s) -
Horn Thomas,
Connolly Michael D.,
Zuckermann Ronald N.
Publication year - 2019
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23268
Subject(s) - phosphoramidate , chemistry , phosphonate , synthon , combinatorial chemistry , sequence (biology) , polymer , solid phase synthesis , reagent , amide , side chain , amine gas treating , diol , polymer chemistry , organic chemistry , stereochemistry , peptide , biochemistry
There is a growing interest in new methods to generate bio‐inspired, chemically diverse, sequence‐defined synthetic polymers. Solid‐phase submonomer approaches offer facile access to these types of materials, since they take advantage of readily available synthons. Submonomer approaches to date have been applied to peptidomimetics with oligo‐amide backbones. Here we extend the approach to a phosphorous‐containing backbone, where N ‐substituted phosphoramidate oligomers are constructed from a set of amine submonomers, diphenyl H‐phosphonate, and cyclohexane diol. The key chemical steps in chain elongation are a chain extension reaction based on H‐phosphonate (P III) chemistry, and a side chain attachment step based on the Atherton‐Todd reaction. Cheap, stable chemical reagents are used without heating, all reaction times are 30 minutes or less and open to air, and no main‐chain protecting groups are required. Phosphoramitoid tetramers and pentamers displaying a variety of side chain functionalities were synthesized by a three‐step solid‐phase submonomer method, typically with >85% crude purities.