Title: Controlled cyclization of peptoids to form chiral diketopiperazines

Abstract

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.

Inventors:

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

Issue Date:

2021-08-10

Research Org.:

Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE National Nuclear Security Administration (NNSA)

OSTI Identifier:

1840327

Patent Number(s):

11084794

Application Number:

16/668,444

Assignee:

Triad National Security, LLC (Los Alamos, NM)

Patent Classifications (CPCs):

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07D - HETEROCYCLIC COMPOUNDS

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C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07D - HETEROCYCLIC COMPOUNDS

C07D241/08 - with oxygen atoms directly attached to ring carbon atoms

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DOE Contract Number:  

89233218CNA000001

Resource Type:

Patent

Resource Relation:

Patent File Date: 10/30/2019

Country of Publication:

United States

Language:

English