Gamma amino acid building blocks

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 alpha-substituted-gamma-nitro-aldehydes. The reaction can be re...

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Bibliographic Details
Main Authors GELLMAN SAMUEL HELMER, GUO LI, GIULIANO MICHAEL
Format Patent
LanguageEnglish
Published 04.03.2014
Subjects
ACYCLIC OR CARBOCYCLIC COMPOUNDS
CHEMISTRY
HETEROCYCLIC COMPOUNDS
METALLURGY
ORGANIC CHEMISTRY
PEPTIDES
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Summary: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 alpha-substituted-gamma-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 gamma-amino acid residues, which are essential for systematic conformational studies of gamma-peptide foldamers. New methods are also provided to prepare other gamma-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as alpha/gamma-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.
Bibliography:Application Number: US20100904942