Syn th esis of Ch ir a l â3-Am in oxy P ep tid es
Dan Yang,*,†,‡ Yu-Hui Zhang,† Bing Li,† and Dan-Wei Zhang†,‡
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China, and
Department of Chemistry, Fudan University, Shanghai, China
yangdan@hku.hk
Received May 16, 2004
A series of chiral â3-aminoxy acids or amides with various side chains have been synthesized via
two different approaches. One is the Arndt-Eistert homologation approach, using chiral R-aminoxy
acids as starting materials. The other approach, utilizing the enantioselective reduction of â-keto
esters catalyzed by baker’s yeast or chiral Ru(II) complexes, produces chiral â3-aminoxy acids with
nonproteinaceous side chains. The oligomers of â3-aminoxy acids can be readily prepared using
EDCI/HOAt as the coupling reagent.
In tr od u ction
Furthermore, homochiral and heterochiral oligomers of
R-aminoxy acids formed novel 1.88 helices and reverse
turns, respectively.5 Compared with R-aminoxy acids,
â-aminoxy acids have an extra carbon atom in the
backbone, thus allowing for more variations in the
substitution patterns of peptides and offering opportuni-
ties to modulate hydrogen-bonding properties. Similar to
â-amino acids, â-aminoxy acids can be divided into
several subclasses according to their backbone substitu-
Due to the interest in structural modifications of
R-amino acids, there have been numerous explorations
of unnatural oligomers with well-defined secondary
structures (foldamers).1 Extensive studies have indicated
that â-peptides and γ-peptides, analogues of R-peptides,
can adopt discrete secondary structures that are analo-
gous to the secondary structures (including helices, turns,
and sheets) found in proteins and peptides.2,3
tion patterns (Chart 1). We have reported that â2,2
-
In our endeavor to search for novel foldamers, R-ami-
noxy peptides and â-aminoxy peptides were designed by
replacing the â-carbon of â-amino acids and the γ-carbon
of γ-amino acids, respectively, with an oxygen atom.
Previous studies of our group have revealed a strong
eight-membered-ring hydrogen bond formed between
adjacent R-aminoxy acid residues (the R-N-O turn).4
aminoxy peptides of 3-aminoxy-2,2-dimethyl propionic
acid can adopt a helical conformation that has ap-
proximately 1.7 residues per turn and contains a network
of nine-membered-ring hydrogen bonds between back-
bone CdOi and NHi+2 (1.79 helix).6a Our recent studies
showed that the â-N-O turns and â-N-O helices, which
have been found in peptides of â2,2-aminoxy acids, are
also present in the â3-aminoxy peptides. Also, in the
â-N-O turns and â-N-O helices induced by â3-aminoxy
acids, the N-O bond could be either anti or gauche to
the CR-Câ bond depending on the size of the side chains,
* Author to whom correspondence should be addressed.
† The University of Hong Kong.
‡ Fudan University.
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10.1021/jo049174f CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/23/2004
J . Org. Chem. 2004, 69, 7577-7581
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