It should be noted that the formation of 4-substituted
2-aryl-4H-1,3,4-oxadiazin-5(6H)-ones was not observed when
acyl hydrazides were employed as the nucleophile in the halide
displacement step. This suggests that while acyl hydrazides are
sufficiently nucleophilic to participate in the desired bromide
displacement reaction, they are not sufficiently basic to depro-
tonate the hydrazide nitrogen on the previous residue.
We have not yet attempted to study in detail the three-
dimensional conformations of acyl hydrazide-derived peptoids,
other than to probe the amide bond geometry and to learn
from the crystal structure of 1d that, at least in the solid state,
the side chain prefers to sit almost orthogonal to the peptoid
main chain, as one might have expected from inspection from
models. However, it should be mentioned that some unusual
characteristics of the NMR spectra of these compounds hint
that they likely exhibit additional interesting structural
features. The 1H NMR spectra of compounds 1a–1d were
comprised of sharp, well-defined peaks with a striking
exception. At room temperature, the methylene (CH2) proton
resonances were very broad in CDCl3 and were not observed
at all in DMSO-d6 (see the ESIw). This cannot be ascribed to
exchange with solvent. When the compounds were incubated
in D2O and then analyzed by high-resolution mass spectro-
metry, no detectable exchange of these methylene protons was
observed (see the ESIw).
structure of a compound displayed on a single bead can be
determined by tandem mass spectrometry. Thus, these new
libraries can be employed in the various powerful screening
platforms developed over the last few years for TentaGel-
displayed OBOC libraries.15
Notes and references
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broad singlet at 25 1C in CDCl3 whereas the other set of
methylene protons (set a) were completely missing. However,
1
low temperature H NMR experiments clearly showed both
the sets (a and b) methylene protons. Interestingly, both these
sets of protons were found to be diastereotopic and geminal
1
couplings were clearly evident from the H spectra.
The 1H NMR spectra of the compounds 4a–4c shows a
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conformational states for N-azapeptoids that are in intermediate
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In conclusion, we have shown that acyl hydrazides can be
used efficiently as sub-monomers to generate peptoid oligo-
mers with trans-amide bond geometries. The presence of
hydrogen bond donor and acceptor units in the side chain
may prove useful in engaging protein targets. While N-azaacyl
units cannot be imbedded into a chain of standard peptoids
efficiently due competing ring closure, one can take advantage
of this reaction to create N-azaacyl peptoids capped with
diverse 2-aryl-4H-1,3,4-oxadiazin-5(6H)-ones. We have
demonstrated that all of this chemistry is compatible with
the synthesis of high quality OBOC libraries and that the
c
10592 Chem. Commun., 2011, 47, 10590–10592
This journal is The Royal Society of Chemistry 2011