Controlled cyclization of peptoids to form chiral diketopiperazines

Williams, Robert F.; Peterson, Paul William; Gilbertson, Robert David; Schmidt, Jurgen G.; Strauss, Charlie E.

Controlled cyclization of peptoids to form chiral diketopiperazines

Patent · Tue Aug 10 00:00:00 EDT 2021

OSTI ID:1840327

Williams, Robert F.; Peterson, Paul William; Gilbertson, Robert David; Schmidt, Jurgen G.; Strauss, Charlie E.

The present disclosure provides improved methods for controlled cyclization of peptoid dimers to form N,N′-2,5-diketopiperazines (N,N′-2,5-DKPs) with significant selectivity. In at least some examples, selectivity is based on a serendipitous conglomeration of slow exchange of amide rotamers, steric repulsion from the degree of α-substitution, and the geometric bulk of an amine nucleophile. By varying reaction conditions, the selectivity of the reaction and formation of a particular N,N′-2,5-DKP can be switched. The cyclization works in the presence of a variety of protection groups and diverse functionalities. The teachings herein provide techniques for synthesizing N,N′-2,5-DKPs that can be readily docked with drug candidates for shuttling across the blood brain barrier. This method provides a facile way to produce substituted DKPs containing groups ready for post-modification to include docking drug candidates.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA)

DOE Contract Number:: 89233218CNA000001

Assignee:: Triad National Security, LLC (Los Alamos, NM)

Patent Number(s):: 11,084,794

Application Number:: 16/668,444

OSTI ID:: 1840327

Country of Publication:: United States

Language:: English

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