Stereocontrolled synthesis of syn-ß-Hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide.
Angew Chem Int Ed Engl
; 53(18): 4642-7, 2014 Apr 25.
Article
em En
| MEDLINE
| ID: mdl-24692320
ABSTRACT
ß-Hydroxy-α-amino acids figure prominently as chiral building blocks in chemical synthesis and serve as precursors to numerous important medicines. Reported herein is a method for the synthesis of ß-hydroxy-α-amino acid derivatives by aldolization of pseudoephenamine glycinamide, which can be prepared from pseudoephenamine in a one-flask protocol. Enolization of (R,R)- or (S,S)-pseudoephenamine glycinamide with lithium hexamethyldisilazide in the presence of LiCl followed by addition of an aldehyde or ketone substrate affords aldol addition products that are stereochemically homologous with L- or D-threonine, respectively. These products, which are typically solids, can be obtained in stereoisomerically pure form in yields of 55-98 %, and are readily transformed into ß-hydroxy-α-amino acids by mild hydrolysis or into 2-amino-1,3-diols by reduction with sodium borohydride. This new chemistry greatly facilitates the construction of novel antibiotics of several different classes.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aminoácidos
/
Glicina
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Anfetaminas
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article