Chemo-, regio- and stereospecific synthesis of unnatural, fluorescent amino acids by condensation of l-lysine and 1-vinylpyrrole-2-carbaldehydes

Article abstract of DOI:10.1002/ejoc.201000620

A new family of unnatural, optically active amino acids containing the pyrrole moiety have been synthesized by condensation of 1-vinylpyrrole-2- carbaldehydes with L-lysine under mild conditions (EtOH, room temp., 2.5-3 h, 0.5 wt.-% of CF₃CO₂H) in up to 90% yields. Unlike non-vinylated analogues, 1-vinylpyrrole-2-carbaldehydes react chemo-, regio- and stereospecifically with an ε-amino group only to afford products of exclusively (E) configuration. The amino acids synthesized containing aromatic or condensed aromatic substitutents in the pyrrole ring fluoresce in the UV/Vis region (γ_max = 350-382 nm, Stokes shifts 6150-7800 cm ^-1).

Full text of DOI:10.1002/ejoc.201000620

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201000620
Chemo-, Regio- and Stereospecific Synthesis of Unnatural, Fluorescent Amino
Acids by Condensation of -Lysine and 1-Vinylpyrrole-2-carbaldehydes
L
Andrey V. Ivanov,[a] Igor A. Ushakov,[a] Konstantin B. Petrushenko,[a] Al’bina I. Mikhaleva,[a]
and Boris A. Trofimov*[a]
Keywords: Amino acids / Aldehydes / Nitrogen heterocycles / Schiff bases / Fluorescence
A new family of unnatural, optically active amino acids con-
taining the pyrrole moiety have been synthesized by conden-
sation of 1-vinylpyrrole-2-carbaldehydes with L-lysine under
mild conditions (EtOH, room temp., 2.5–3 h, 0.5 wt.-% of
CF3CO2H) in up to 90% yields. Unlike non-vinylated ana- (λmax = 350–382 nm, Stokes shifts 6150–7800 cm–1).
and stereospecifically with an ε-amino group only to afford
products of exclusively (E) configuration. The amino acids
synthesized containing aromatic or condensed aromatic sub-
stitutents in the pyrrole ring fluoresce in the UV/Vis region
logues, 1-vinylpyrrole-2-carbaldehydes react chemo-, regio-
ents, now available[11] by formylation of the corresponding
Introduction
1-vinylpyrroles (also accessible[12] compounds) represent
Lysine is known to play key structural and functional
highly reactive[13] building blocks for the introduction of
roles in proteins.[1] The basic side chains of the lysine resi-
diverse pyrrole chromophores to the lysine molecules.
dues are essential in the DNA–protein recognition. Their
almost ubiquitous presence in the interface of DNA–pro-
Here we report on the synthesis of the hitherto unknown
family of unnatural amino acids 2a–f by condensation of -
lysine with 1-vinylpyrrole-2-carbaldehydes 1a–f.
tein complexes makes lysine an attractive target for chemi-
cal modifications.[2] Chemical transformations of the lysine
amino groups are employed in the synthesis of antitumor
drugs[3] and virus suppressors.[4] Similar lysine derivatives
are isolated from natural sources.[5] Such modifications pro-
vide important information of the protein properties, e.g.
Results and Discussion
about the sweetness of lysozyme.[6] The lysine moiety offers
a convenient way of incorporating various chemical groups
onto the protein surfaces.[7] The development of new meth-
odologies to increase the sensitivity of biological imaging in
living cells is now considered as one of the cardinal research
challenges.[8] Therefore, one important application of the ly-
sine modifications is the labelling of synthetic peptides for
monitoring enzyme activity. The introduction of fluorescent
moieties into the lysine molecules is an alternative to the
use of radioactive labels.[9] One of the most expedient and
useful approaches to lysine modifications involves its con-
densation with carbonyl compounds to deliver Schiff
bases.[10] However, to the best of our knowledge, no exam-
ple of a lysine condensation with pyrrole-2-carbaldehydes
has been so far reported, though such a combination could
lead to lysine derivatives possessing fluorescent properties
that might be promising for the design of biological labels.
1-Vinylpyrrole-2-carbaldehydes, particularly those having
aromatic, condensed aromatic or heteroaromatic substitu-
The reaction of -lysine with 1-vinylpyrrole-2-carb-
aldehydes 1a–f proceeds smoothly (EtOH, 0.5 wt.-% of
CF3COOH, room temperature, 2.5–3 h) to give amino acids
2a–f in a chemo-, regio- and stereospecific mode involving
the ε-amino group only (Scheme 1). Schiff bases 2a–f are
formed exclusively in the (E) configuration in 69–90%
yields (Table 1).
Scheme 1. Synthesis of unnatural amino acids 2.
[a] A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch
of the Russian Academy of Sciences,
Likewise, amino acid 2f containing an annulated dihy-
dronaphthalene moiety has been synthesized from 1-vinyl-
4,5-dihydrobenz[g]indole-2-carbaldehyde (1f) (Scheme 2).
1 Favorsky St., Irkutsk 664033, Russian Federation
Fax: +7-3952-419346
E-mail: boris_trofimov@irioch.irk.ru
4554
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4554–4558

Unnatural, Fluorescent Amino Acids
Table 1. Substituents and isolated yields of amino acids 2.
both expected Schiff bases 4 and 5 were isolated in a yield
of 80% (Scheme 3), the ratio 4/5 being 3:1 (1H NMR spec-
troscopy).
Scheme 3. Behaviour of non-vinylated pyrrole-2-carbaldehyde 3 un-
der the conditions studied.
In contrast to N-unsubstituted pyrrole-2-carbaldehyde 3,
in the case of 1-vinylpyrrole-2-carbaldehydes 1a–f, the pos-
sible alternative isomers formed with the participation of
the α-amino group of lysine are not detected, even in trace
concentrations (1H NMR spectroscopy). Since the elec-
tronic effect of the N-vinyl group on the carbonyl function
transmitted through the pyrrole ring proves to be negligible
(13C NMR chemical shifts of the carbonyl carbon atoms in
1a and 3: δ = 178.8 and 178.6 ppm, respectively), a probable
reason of the observed regiospecificity of the Schiff base
formation is the steric hindrance from the N-vinyl group
to the attack of the lysine α-amino group on the carbonyl
function.
Scheme 2.
All amino acids 2a–f exist exclusively as the (E) isomers.
This was confirmed by 2D NOESY experiments, which
show NOE correlations between the HC=N proton and 3-
H of the pyrrole moiety, as well as between the HC=N pro-
ton and the N–CH2 group of the lysine fragment (Figure 1).
The 1-vinylpyrroles with aromatic, condensed aromatic
and heteroaromatic substitutents have been specially se-
lected having in mind their better chromophoric properties
due to the conjugation between the substituents and the
pyrrole ring. This should improve the expected fluorescent
properties of the target amino acids.
For the condensation of -lysine with 1-vinylpyrrole-2-
carbaldehydes 1a–f, we have employed trifluoroacetic acid
(CF3COOH) as catalyst, because our previous investi-
gations have shown[13c] that this acid efficiently and selec-
tively catalyzes the transformations of 1-vinylpyrrole-2-
carbaldehydes to the corresponding Schiff bases, the acido-
phobic N-vinyl group being preserved. The reaction does
not occur without catalyst (GLC data).
Figure 1. Cross-peaks in the 2D NOESY and HMBC spectra of
the amino acids 2.
The (E)/(Z) isomerism around the C=N bond makes
these amino acids potential optical molecular switches due
Lysine is known to participate in a variety of reactions to (E)/(Z) isomerisation under UV irradiation.
(including Schiff base formation) involving both its α- and
A zwitterionic form of the amino acid 2 is supported by
ε-amino groups.[7b,8,14] As a rule, to selectively conduct the its IR (KBr) spectrum, where a broad strong absorption in
reaction by exploiting just one amino group, it is needed to the region of 3300–2500 cm–1 is observed. This absorption
protect the second one.[8,10d,14b,14c] In agreement with these is commonly assigned to the +NH3 group.[15] In the spec-
data, when non-vinylated 1-H-pyrrole-2-carbaldehyde 3 re- trum, a band at 2150–2100 cm–1 is attributable to the same
–
acts with -lysine under the above conditions (Scheme 1), +NH3 moiety. The CO2 anion was spectroscopically con-
Eur. J. Org. Chem. 2010, 4554–4558
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4555

B. A. Trofimov et al.
SHORT COMMUNICATION
techniques were used. IR spectra were recorded with a Bruker IFS
25 spectrometer. All melting points were taken with a Kofler micro
hot stage. Optical rotations were measured with a Polamat A pola-
rimeter at 23 °C. 1-Vinylpyrrole-2-carbaldehydes were obtained ac-
cording to ref.[11b] Other chemicals (Aldrich) and solvents were of
commercial grade.
firmed by a broad absorption in the region of 1650–
1550 cm–1, obviously overlapping with the band of the
C=N and C=C stretching-vibration bands.
Amino acids 2a–f are soluble in DMSO and DMSO/
water (1:1) and scarcely soluble in benzene, acetone, chloro-
form and acetonitrile.
Synthesis of 2-Amino-6-{[(1-vinylpyrrol-2-yl)methylene]amino}-
hexanoic Acids 2a–f: A mixture of 1-vinylpyrrole-2-carbaldehyde 1
(1 mmol), -lysine monohydrate (0.16 g, 1 mmol) and CF3COOH
(0.5 wt.-% with respect to the whole mass) in EtOH (7 mL) was
stirred at room temperature for 2.5–3 h. The residue precipitated
was filtered off, washed with cold water and EtOH and dried.
All the amino acids containing aromatic and condensed
aromatic substituents (2b–e) fluoresce in the near-UV re-
gion (350–362 nm); the amino acid with a naphthyl substut-
ient (2d) emits in a visible spectral region (382 nm). Their
Stokes shifts range from 6150 to 7800 cm–1 (Table 2).
2-Amino-6-{[(1-vinylpyrrol-2-yl)methylene]amino}hexanoic Acid
(2a): From 0.12 g (1 mmol) of 1a 0.17 g (69%) of 2a was obtained.
Beige crystals. M.p. 150–153 °C (decomp.). [α]2D3 = +11.3 (c = 0.02,
CH3CN). 1H NMR (400 MHz, [D6]DMSO): δ = 8.12 (s, 1 H,
CH=N), 7.85 (dd, 3JA-X = 8.7, 3JB-X = 15.5 Hz, 1 H, HX), 7.18 (m,
Table 2. UV/Vis and fluorescence spectra of amino acids 2b–d,f
(MeCN).
Amino acid
Absorption[a]
λmax [nm]
Emission
λmax [nm]
Stokes shift
[cm–1]
3
2b
2c
292
286
279
292
356
350
357, 382(sh.)
362
6150
6400
7800
6600
1 H, 5-H), 6.54 (m, 1 H, 3-H), 6.32 (m, 1 H, 4-H), 5.00 (d, JB-X
3
= 15.5 Hz, 1 H, HB), 4.90 (d, JA-X = 8.7 Hz, 1 H, HA), 3.42 (m, 2
2d[b]
2f
H, NCH2), 3.40 (br. s, 3 H, NH2, OH), 3.11 (m, 1 H, CH), 1.73
(m, 2 H, CH2), 1.58 (m, 2 H, CH2), 1.36 (m, 2 H, CH2) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 169.8 (1 C, C=O), 150.8 (1 C,
C=N), 133.2 (1 C, Cα), 129.4 (1 C, C-2), 120.5 (1 C, C-5), 115.4 (1
C, C-3), 110.3 (1 C, C-4), 105.5 (1 C, Cβ), 60.2 (1 C, NCH2), 54.4
(1 C, CH), 31.6 (1 C, CH2), 29.9 (1 C, CH2), 23.5 (1 C, CH2) ppm.
C13H19N3O2 (249.31): calcd. C 62.63, H 7.68, N 16.85; found C
63.00, H 7.50, N 16.66.
[a] The values are derived from excitation spectra. [b] The emission
spectrum has a vibration structure.
Conclusions
2-Amino-6-{[(5-phenyl-1-vinylpyrrol-2-yl)methylene]amino}hexanoic
Acid (2b): From 0.20 g (1 mmol) of 1b 0.25 g (78%) of 2b was ob-
tained. Beige crystals. M.p. 192–195 °C (decomp.). [α]2D3 = +5.0 (c
A general methodology for the synthesis of a new family
of unnatural amino acids, containing hydrophobic pyrrole-
based chromophores, has been developed. The methodol-
ogy consists of the chemo-, regio- and stereospecific con-
densation of -lysine with 1-vinylpyrrole-2-carbaldehydes
catalyzed by CF3COOH under mild conditions (EtOH,
room temp.). The amino acids synthesized exhibit promis-
ing fluorescent properties and are prospective in the search
for novel biological labels. The methodology allows the
fluorescence parameters to be controlled by employing di-
verse aryl-, hetaryl- and condensed aromatic substituted 1-
vinylpyrroles readily available from ketones and acetylene
by the Trofimov reaction.[12] The amino acids synthesized
according to the above methodology represent a rare com-
bination of pharmacophoric pyrrole and amino acid moie-
ties and hence can also be used as flexible building blocks
for drug design. The reactive N-vinyl group in the molecules
of the amino acids synthesized is of a particular structural
advantage. This makes these compounds promising mono-
mers, which are prone to various addition reactions across
the double bond.[16] A possible combination of vinyl poly-
merization (or cross-linking) with peptide synthesis may ex-
tend considerably the scope of application of these novel
amino acids.
= 0.02, CH CN). IR (KBr): ν = 3444, 3030, 2988, 2855, 2821, 1629,
˜
3
1601, 1514, 1464, 1450, 1400, 1352, 1328, 1288, 1232, 1199, 1156,
1116, 1074, 1043, 1005, 957, 915, 864, 784, 758, 698, 660, 598, 543,
1
512, 494, 453 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 8.23 (s,
3
3
1 H, CH=N), 7.49 (dd, JA-X = 8.6, JB-X = 15.6 Hz, 1 H, HX),
3
7.41 (m, 4 H, Ho, Hm, Ph), 7.32 (m, 1 H, Hp, Ph), 6.71 (d, J3-4
=
3
3.6 Hz, 1 H, 3-H), 6.34 (d, J3-4 = 3.6 Hz, 1 H, 4-H), 5.09 (d,
3JA-X = 8.6 Hz, 1 H, HA), 4.72 (d, JB-X = 15.6 Hz, 1 H, HB), 3.46
3
(m, 2 H, NCH2), 3.40 (br. s, 3 H, NH2, OH), 3.12 (m, 1 H, CH),
1.74 (m, 2 H, CH2), 1.58 (m, 2 H, CH2), 1.37 (m, 2 H, CH2) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 169.9 (1 C, C=O), 151.9 (1
C, C=N), 136.8 (1 C, C-5), 132.3 (1 C, Ci), 132.0 (1 C, Cα), 131.5
(1 C, C-2), 128.6 (2 C, Co), 128.4 (2 C, Cm), 127.3 (1 C, Cp), 114.9
(1 C, C-3), 111.5 (1 C, C-4), 111.3 (1 C, Cβ), 61.0 (1 C, NCH2),
54.2 (1 C, CH), 31.0 (1 C, CH2), 30.7 (1 C, CH2), 23.1 (1 C, CH2)
ppm. C19H23N3O2 (325.41): calcd. C 70.13, H 7.12, N 12.91; found
C 70.15, H 7.06, N 12.72.
2-Amino-6-{[5-(4-methoxyphenyl)-1-vinylpyrrol-2-yl)methylene]-
amino}hexanoic Acid (2c): From 0.23 g (1 mmol) of 1c 0.32 g (89%)
of 2c was obtained. Orange crystals. M.p. 179–183 °C (decomp.).
[α]2D3 = +4.9 (c = 0.02, CH CN). IR (KBr): ν = 3439, 3036, 2988,
˜
3
2853, 1628, 1610, 1581, 1516, 1468, 1432, 1406, 1352, 1329, 1309,
1288, 1251, 1199, 1179, 1158, 1130, 1111, 1043, 1029, 973, 959,
919, 857, 837, 795, 769, 736, 721, 698, 663, 631, 606, 591, 530,
451 cm–1 1H NMR (400 MHz, [D6]DMSO): δ = 8.21 (s, 1 H,
.
CH=N), 7.48 (dd, 3JA-X = 8.8, 3JB-X = 15.6 Hz, 1 H, HX), 7.34 (m,
Experimental Section
3
2 H, Ho, Ph), 6.98 (m, 2 H, Hm, Ph), 6.68 (d, J3-4 = 3.6 Hz, 1 H,
General: 1H (400.13 MHz) and 13C (101.6 MHz) NMR spectra 3-H), 6.25 (d, J3-4 = 3.6 Hz, 1 H, 4-H), 5.07 (d, JA-X = 8.6 Hz, 1
3
3
3
were recorded with Bruker DPX 400 or AV-400 spectrometers by
using hexamethyldisiloxane (HMDS) as an internal standard. In
H, HA), 4.73 (d, JB-X = 15.6 Hz, 1 H, HB), 3.78 (s, 3 H, OMe),
3.46 (m, 2 H, NCH2), 3.30 (br. s, 3 H, NH2, OH), 3.09 (m, 1 H,
CH), 1.75 (m, 2 H, CH2), 1.56 (m, 2 H, CH2), 1.36 (m, 2 H, CH2)
ppm. 13C NMR (100 MHz, [D6]DMSO): δ = 169.7 (1 C, C=O),
1
order to attribute H and 13C peaks, 2D homonuclear COSY and
NOESY routines, as well as 2D heteronuclear HSQC and HMBC
4556
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4554–4558

Unnatural, Fluorescent Amino Acids
160.3 (1 C, Ci), 154.9 (1 C, C=N), 138.2 (1 C, C-5), 134.3 (1 C, Ci), [D6]DMSO): δ = 169.7 (1 C, C=O), 152.0 (1 C, C=N), 136.2 (1 C,
132.1 (1 C, Cα), 131.9 (2 C, Cm), 131.7 (1 C, C-2), 115.7 (2 C, Co), Car), 133.2 (1 C, Cα), 132.0 (1 C, C-2), 131.9 (1 C, Car), 130.9 (1 C,
114.6 (1 C, C-3), 112.1 (1 C, C-4), 111.7 (1 C, Cβ), 61.2 (1 C, C-5), 128.3, 127.2, 126.1, 125.6 (4 C, CHar), 125.4 (1 C, C-4), 111.4
NCH2), 56.4 (1 C, OMe), 54.5 (1 C, CH), 31.2 (1 C, CH2), 30.5 (1
C, CH2), 22.9 (1 C, CH2) ppm.
(1 C, C-3), 111.0 (1 C, Cβ), 60.4 (1 C, NCH2), 54.5 (1 C, CH), 30.8
(1 C, CH2), 29.9 (1 C, CH2), 29.6 (1 C, CH2), 23.1 (1 C, CH2), 21.8
(1 C, CH2) ppm. C21H25N3O2 (351.45): calcd. C 71.77, H 7.17, N
11.96; found C 71.88, H 7.21, N 11.86.
2-Amino-6-[(5-naphthalen-2-yl-1-vinylpyrrole-2-ylmethylidene)-
amino]hexanoic Acid (2d): From 0.25 g (1 mmol) of 1d 0.29 g (77%)
of 2d was obtained. Beige crystals. M.p. 208–211 °C (decomp.).
[α]2D3 = +3.2 (c = 0.02, CH CN). IR (KBr): ν = 3441, 3050, 2934,
˜
3
Acknowledgments
2858, 1636, 1582, 1515, 1452, 1407, 1355, 1325, 1302, 1273, 1257,
1215, 1195, 1158, 1130, 1046, 1016, 977, 959, 948, 926, 892, 858,
817, 779, 761, 742, 681, 665, 651, 632, 590, 552, 533, 474, 450 cm–1.
This work has been carried out under financial support of leading
1H NMR (400 MHz, [D6]DMSO): δ = 8.26 (s, 1 H, CH=N), 7.99 scientific schools by the President of the Russian Federation (Grant
3
3
(s, 1 H, Har), 7.90 (m, 3 H, Har), 7.61 (dd, JA-X = 8.6, JB-X
=
NSH-3230.2010.3)
15.6 Hz, 1 H, HX), 7.55 (m, 3 H, Har), 6.75 (d, 3J3-4 = 3.8 Hz, 1 H,
3-H), 6.48 (d, J3-4 = 3.8 Hz, 1 H, 4-H), 5.11 (d, JA-X = 8.6 Hz, 1
H, HA), 4.74 (d, JB-X = 15.6 Hz, 1 H, HB), 3.48 (m, 2 H, NCH2),
3
3
3
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H, 3Ј-H), 7.34 (dd, JA-X = 8.6, JB-X = 15.9 Hz, 1 H, HX), 7.20
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pp. 55–89; d) Z. Wang, in: Comprehensive Organic Name Reac-
tions and Reagents, Wiley, London, 2009, paragraph 626.
[13] a) A. M. Vasil’tsov, A. V. Ivanov, I. A. Ushakov, A. I. Mikh-
aleva, B. A. Trofimov, Synthesis 2007, 452–456; b) B. A. Trofi-
mov, A. V. Ivanov, E. V. Skital’tseva, A. M. Vasil’tsov, I. A.
Ushakov, K. B. Petrushenko, A. I. Mikhaleva, Synthesis 2009,
3603–3610; c) A. I. Mikhaleva, A. V. Ivanov, A. M. Vasil’tsov,
I. A. Ushakov, J. S. Ma, G. Yang, Chem. Heterocycl. Compd.
2008, 1117–1123.
3
3.4 Hz, 1 H, 4Ј-H), 6.71 (d, J3-4 = 3.9 Hz, 1 H, 3-H), 6.42 (d,
3J3-4 = 3.9 Hz, 1 H, 4-H), 5.33 (d, JA-X = 8.6 Hz, 1 H, HA), 5.08
3
3
(d, JB-X = 15.9 Hz, 1 H, HB), 3.46 (m, 2 H, NCH2), 3.40 (br. s, 3
H, NH2, OH), 3.08 (m, 1 H, CH), 1.73 (m, 2 H, CH2), 1.55 (m, 2
H, CH2), 1.35 (m, 2 H, CH2) ppm. 13C NMR (100 MHz, [D6]-
DMSO): δ = 169.7 (1 C, C=O), 151.9 (1 C, C=N), 133.8 (1 C, C-
2Ј), 132.1 (1 C, Cα), 132.0 (1 C, C-5), 129.9 (1 C, C-2), 127.7 (1 C,
C-3Ј), 127.5 (1 C, C-4Ј), 126.7 (1 C, C-5Ј), 114.1 (1 C, C-3), 113.9
(1 C, Cβ), 112.1 (1 C, C-4), 61.1 (1 C, NCH2), 54.3 (1 C, CH), 31.1
(1 C, CH2), 30.6 (1 C, CH2), 23.2 (1 C, CH2) ppm. C17H21N3O2S
(331.43): calcd. C 61.61, H 6.39, N 12.68; found C 61.89, H 6.11,
N 12.82.
2-Amino-6-{[(1-vinyl-4,5-dihydrobenzo[g]indol-2-yl)methylene]-
amino}hexanoic Acid (2f): From 0.22 g (1 mmol) of 1f 0.30 g (85%)
of 2f was obtained. Beige crystals. M.p. 206–210 °C (decomp.).
[α]2D3 = +5.5 (c = 0.01, CH CN). IR (KBr): ν = 3446, 3055, 2931,
˜
3
1628, 1603, 1583, 1515, 1478, 1439, 1407, 1358, 1324, 1308, 1294,
1254, 1194, 1158, 1135, 1097, 1046, 1026, 980, 916, 808, 775, 757,
1
736, 712, 668, 652, 509, 467, 442, 421 cm–1. H NMR (400 MHz,
3
[D6]DMSO): δ = 8.18 (s, 1 H, CH=N), 7.55 (dd, JA-X = 8.3,
3JB-X = 15.6 Hz, 1 H, HX), 7.59 (m, 1 H, Har), 7.27 (m, 1 H, Har),
7.18 (m, 1 H, Har), 7.10 (m, 1 H, Har) 6.60 (s, 1 H, 3-H), 5.38 (d,
3
3JA-X = 8.3 Hz, 1 H, HA), 5.18 (d, JB-X = 15.6 Hz, 1 H, HB), 3.46
(m, 2 H, NCH2), 3.40 (br. s, 3 H, NH2, OH), 3.10 (m, 1 H, CH),
2.78 (m, 2 H, CH2), 2.54 (m, 2 H, CH2), 1.72 (m, 2 H, CH2), 1.54
(m, 2 H, CH2), 1.36 (m, 2 H, CH2) ppm. 13C NMR (100 MHz,
[14] a) R. M. Freidinger, J. Org. Chem. 1985, 50, 3631–3633; b) R.
Alsfasser, R. Van Eldik, Inorg. Chem. 1996, 35, 628–636; c) E.
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www.eurjoc.org
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aleva, M. V. Markova, Makromol. Chem. 1987, 188, 2251–
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Markova, L. V. Morozova, E. Yu. Schmidt, E. Yu. Senotru-
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Received: May 4, 2010
Published Online: July 16, 2010
4558
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4554–4558