Deconstructive Diversification Of Cyclic Amines Useful For Proline Tagging
Tech ID: 31707 / UC Case 2018-187-0
A deconstructive strategy to transform saturated nitrogen heterocycles such as piperidines and pyrrolidines into halogen-containing acyclic amine derivatives through sequential Csp3–N/Csp3–Csp3 single bond cleavage followed by Csp3–halogen bond formation. The resulting acyclic haloamines serve as versatile intermediates that are expediently transformed into a variety of structural motifs through substitution reactions. In this way, skeletal remodeling, which constitutes a scaffold hop, can be achieved. The value of this deconstructive strategy has been demonstrated through the late-stage diversification of proline-containing peptides, thus achieving late-stage proline tagging.
Tagging of prolines on proteins and peptides to allow the addition of payloads and diversification of peptides in DNA encoded libraries. This is an area of interest to pharmaceutical companies.