Michael A Giuliano

US Patent:

20160280632, Sep 29, 2016

Filed:

Jun 6, 2016

Appl. No.:

15/174306

Inventors:

- Madison WI, US
Li Guo - Blue Bell PA, US
Michael Giuliano - Derby CT, US

Assignee:

WISCONSIN ALUMNI RESEARCH FOUNDATION - Madison WI

International Classification:

C07C 205/44
C07C 205/55
C07C 201/12

Abstract:

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.).The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected γ-amino acid residues, which are essential for systematic conformational studies of γ-peptide foldamers. New methods are also provided to prepare other γ-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as α/γ-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.

US Patent:

20150148523, May 28, 2015

Filed:

Jan 28, 2014

Appl. No.:

14/166007

Inventors:

- Madison WI, US
Li Guo - Blue Bell PA, US
Michael Giuliano - Derby CT, US

Assignee:

Wisconsin Alumni Research Foundation - Madison WI

International Classification:

C07K 7/06
C07C 271/66
C07C 205/55
C07C 269/00
C07K 5/065
C07K 5/107
C07C 201/12
C07C 205/44
C07C 271/24

US Classification:

530329, 568423, 560115, 562507, 560125, 530330

Abstract:

The invention provides compounds and methods, for example, to carry out organocatalytic Michael additions of aldehydes to cyclically constrained nitroethylene compounds catalyzed by a proline derivative to provide cyclically constrained α-substituted-γ-nitro-aldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96 to >99% e.e.).The Michael adducts can bear a single substituent or dual substituents adjacent to the carbonyl. The Michael adducts can be efficiently converted to cyclically constrained protected γ-amino acid residues, which are essential for systematic conformational studies of γ-peptide foldamers. New methods are also provided to prepare other γ-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as α/γ-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.