Wisconsin Alumni Research Foundation

Li Guo

Samuel Helmer Gellman

Yonggui Chi

Michael Giuliano

William Seth Horne

William C Pomerantz

Emily P English

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 &#x3b1;-substituted-&#x3b3;-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 &#x3e;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 &#x3b3;-amino acid residues, which are essential for systematic conformational studies of &#x3b3;-peptide foldamers. New methods are also provided to prepare other &#x3b3;-amino acids and peptides. These new building blocks can be used to prepare foldamers, such as &#x3b1;/&#x3b3;-peptide foldamers, that adopt specific helical conformations in solution and in the solid state.

Gamma amino acid building blocks

The invention provides novel compounds and methods to carry out organocatalytic Michael additions of aldehydes to nitroethylene catalyzed by a proline derivative to provide &#x3b1;-substituted-&#x3b3;-nitroaldehydes. The reaction can be rendered enantioselective when a chiral pyrrolidine catalyst is used, allowing for Michael adducts in nearly optically pure form (e.g., 96-99% 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 protected &#x3b3;-amino acids, which are essential for systematic conformational studies of &#x3b3;-peptide foldamers.

Methods for preparing amides and amino acids

Amino acids and catalytic preparatory methods

The present invention provides a method for the synthesis of &#x3b2;-amino acids. The method also provides methods yielding &#x3b1;-substituted &#x3b2;-amino aldehydes and &#x3b2;-substituted &#x3b3;-amino alcohols. The present method according to this invention allows for increased yield and easier purification using minimal chromatography or crystallization. The methods described herein are based on an aldehyde aminomethylation which involves a Mannich reaction between an aldehyde and a formaldehyde-derived N,O-acetal (iminium precursor) and a catalyst, such as, for example, L-proline or a pyrrolidine. The invention allows for large scale, commercial preparation of &#x3b2;-amino acids.

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Li Guo