Organo catalytic strategies towards α, α [alpha, alpha] disubstituted amino acid derivatives

Autori

• Henning Vogt

Parametri

• Libri di testo
• Libri di testo universitari

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The class of non-proteinogenic α,α-disubstituted amino acids and their derivatives is significant in biochemical and pharmacological research due to their ability to modify the chemical and physicochemical properties of peptides. Their structural similarity to biologically relevant amino acid derivatives allows them to function as enzyme inhibitors or receptor antagonists. This study presents new strategies for synthesizing N-protected α,α-disubstituted amino aldehydes and their derivatives. Starting from ketones, α,α-disubstituted aldehydes were synthesized in two or three steps and then subjected to stereoselective organo-catalyzed α-amination reactions. A procedure for α-aminating α-unbranched aldehydes was adapted for racemic α-branched aldehydes, yielding N-protected aminoaldehydes with up to 87% yield and 86% enantiomeric excess (ee). The amination products were converted to N-protected 4,4-disubstituted oxazolidinones after in situ reduction. Additionally, a novel strategy using sulfonyl azides as aminating agents produced α-sulfamidated α,α-disubstituted aldehydes with yields up to 55% and 86% ee. A proposed mechanism differs from the typical enamine catalysis model. The sulfamidation product was transformed into the free amino acid in two steps. These strategies, following different mechanistic routes, allow access to diverse enantiomers using one catalyst and are free of transition metals, making them particularly be

Lingua: Inglese

Pubblicato: 2006

(In brossura)