Dipeptides with 3-(trimethylstannyl)alanine building blocks: Synthesis, characterization, and reactivity

Article abstract of DOI:10.1007/s00706-012-0902-6

3-(Trimethylstannyl)alanine esters containing a free amino group react with different N-benzoyloxycarbonyl amino acids in the presence of N,N′-dicyclohexylcarbodiimide to yield new dipeptides with β-(trimethylstannyl)alanine building blocks. Reactions at the stannyl group were studied in more detail in two glycyl alaninates. Their reaction with Me₃SnCl without solvent yields the chlorostannyl-substituted compounds. The glycyl alaninates react with two equivalents of bromine to give the dibromostannylated compounds.

Full text of DOI:10.1007/s00706-012-0902-6

Monatsh Chem (2013) 144:729–734
DOI 10.1007/s00706-012-0902-6
ORIGINAL PAPER
Dipeptides with 3-(trimethylstannyl)alanine building blocks:
synthesis, characterization, and reactivity
¨
Karin Dolling
Received: 10 September 2012 / Accepted: 9 December 2012 / Published online: 31 January 2013
Ó Springer-Verlag Wien 2013
Abstract 3-(Trimethylstannyl)alanine esters containing a
free amino group react with different N-benzoyloxycarbonyl
amino acids in the presence of N,N0-dicyclohexylcarbodiimide
to yield new dipeptides with b-(trimethylstannyl)alanine
building blocks. Reactions at the stannyl group were studied in
more detail in two glycyl alaninates. Their reaction with
Me3SnCl without solvent yields the chlorostannyl-substituted
compounds. The glycyl alaninates react with two equivalents
of bromine to give the dibromostannylated compounds.
with nitrogen and/or oxygen atoms of functional groups.
Diorganotin(IV) derivatives of different dipeptides have been
synthesized by the reaction of diorganotin dichloride with the
sodium salt of various dipeptides [15, 16]. In these diorgano-
tin(IV) dipeptides the tin atom is coordinated with the
dipeptide through the COO-, NH2, and Npeptide groups. In
triorganotin(IV) dipeptides synthesized by reaction of bis(tri-
organotin)oxide and the appropriate N-acetylpeptide using
dehydrating agents [17] or by reaction of triorganotin(IV)
chlorides with the sodium salt of N-protected dipeptides [18],
the tin atom is coordinated by the carboxylic group and by the
oxygen atom of the amidocarbonyl group. Only very few tin-
containing dipeptides are known, prior to the current article, in
which the tin atom is directly bound to carbon. One example is
the product of palladium-catalyzed stanna-allylation of the a-
CH2 group of different dipeptides [19]. These stannylated
dipeptides possess a large synthetic potential regarding side-
chain modifications or conversion into the iodo derivatives by
metal–halogen exchange. A second example is the synthesis of
N-Boc-p-(tri-n-butylstannyl)-L-phenylalanine tetrafluorophe-
nyl ester [20] starting from N-Boc-p-iodo-L-phenylalanine and
bis(tributyltin).
Keywords Tin compounds ꢀ Bioinorganic chemistry ꢀ
Amino acids ꢀ Peptides ꢀ NMR spectroscopy
Introduction
Organotin compounds of dipeptides have been well known for
someyears [1]. The mostthoroughly investigated examples are
the di- and triorganotin derivatives of glycylglycine and of
alanylglycine [2–6]. In the last 20 years numerous tri- and
diorganotin dipeptides were synthesized and their biological
properties tested [7–11]. The stannylated dipeptides mostly
have been screened for antitumor, anti-inflammatory, and
cardiovascular activities [12]. A review of the antimicrobial
activity of organotin(IV) compounds including numerous
dipeptides [13] was recently published as was a review on the
toxicity and cardiovascular activity [14]. The tin atom in all the
compounds described in the aforementioned reports and in
nearly all stannylated dipeptides known so far is coordinated
Our research into C-stannylated amino acid derivatives [21,
22] was extended to C-stannylated dipeptides, which can be
synthesized from 3-(trimethylstannyl)alanine esters which
have a free amino group [23]. This C-stannylated alanine could
be obtained by reaction of N-(diphenylmethylene)glycineester
with iodomethyl triorganostannanes. The resulting 3-(triorg-
anostannyl)-N-(diphenylmethylene)alanine ester could be
transformed by mild two-phase hydrolysis to 3-(triorgano-
stannyl)alanine ester hydrochloride. The corresponding
alanine ester was obtained after treatment with NH3 in chlo-
roform, but these compounds were of limited stability.
With the alanine esters in hand we next investigated whether
the stability of the 3-(trimethylstannyl)alanine esters was
¨
K. Dolling (&)
Martin-Luther-Universitat Halle, Biozentrum,
¨
06099 Halle, Germany
e-mail: karin.doelling@web.de;
karin.doelling@medizin.uni-halle.de
123

730
K. Dolling
1
nevertheless sufficient for further reactions. This issue should
be answered by these studies.
dipeptides 3 were characterized by elemental analysis, H
and 119Sn NMR spectroscopy, and IR spectroscopy.
The starting b-(trimethylstannyl)alanine esters were
used as a racemic mixture. The product of reaction of this
racemic mixture with derivatives of achiral glycine yield
3a–3d as a racemic mixture also. Their 119Sn NMR spectra
show only one single signal and the proton NMR spectra
show sharp signals without any splitting.
In our research we were encouraged by two points: first,
the reported anticancer activity of stannylated dipeptides
with Sn–O/N coordination [24] and second it should be
interesting to compare these known compounds with
C-stannylated ones in the light of the hypothesis that the
antileukemic activity of organotin compounds is due to the
formation of R3Sn(IV) species as a result of hydrolytic
processes [25].
In the case of synthesis of 3e–3j the results are more
complicated. Since these new molecules contain two ste-
reocenters the products should be mixtures of
diastereoisomers. This can be seen in the 119Sn NMR
spectra which are well separated into two signals
(Dd = 0.26–0.37 ppm) of nearly equal intensity. Also, the
1H NMR signals are split. After column chromatography
and fractional crystallization the isomers could be isolated.
These isolated isomers were characterized by NMR data
given in the ‘‘Experimental’’. Their stereochemistry is not
yet finally determined.
We describe here our first results on the synthesis and
reactivity of C-stannylated dipeptides with 3-(trimethyl-
stannyl)alanine building blocks.
Results and discussion
There are numerous methods to synthesize dipeptides
starting from amino acids containing a free amino group.
For the synthesis of stannylated dipeptides it seemed useful
to adopt the carbodiimide method based on Shehan and
Hess’s work [26]. The synthesis of 3-(trimethylstan-
nyl)alanine derivatives of glycine (R1 = H, 3a–3d),
L-alanine (R1 = CH3, 3e, 3f), D,L-valine (R1 = CH(CH3)2,
3g, 3h), and L-phenylalanine (R1 = CH2Ph, 3i, 3j)
succeeded in good yields (Scheme 1).
1
The assignments of H resonances are in accordance
with literature values for the dipeptides without tin sub-
stituents [27] and the integration areas are equivalent to the
number of protons.
The 119Sn NMR shift of these dipeptides is situated in
the region for tetramethyltin compounds [28] indicating a
tetra-coordination at the tin atom. There are no interactions
between tin and the functional groups of the rest of the
molecule. The spectroscopic data are given in the
‘‘Experimental’’.
The stannylated dipeptides 3 are colorless, low melting
solids which are very soluble in halogenated hydrocarbons
and diethyl ether, but less soluble in hydrocarbons. The
R1
O
Scheme 1
O
O
R1
O
O
O
NH
R2
O
O
NH
R2
O
O
+
H2N
HN
OH
Sn
Sn
1a-1d
2a-2d
3a-3j
a: R1 = Me
b: R1 = Et
c: R1 = Bz
d: R1 = t-Bu
a: R2 = H (gly)
b: R2 = CH3 (L-ala)
c: R2 = CH(CH3)2 (D,L-val)
d: R2 = CH2Ph (L-phe)
a: R1 = Me, R2 = H (gly)
b: R1 = Et, R2 = H (gly)
c: R1 = Bz, R2 = H (gly)
d: R1 = t-Bu, R2 = H (gly)
e: R1 = Me, R2 = CH3 (L-ala)
f: R1 = Et, R2 = CH3 (L-ala)
g: R1 = Me, R2 = CH(CH3)2 (D,L-val)
h: R1 = Et, R2 = CH(CH3)2 (D,L-val)
i: R1 = Me, R2 = CH2Ph (L-phe)
j: R1 = Et, R2 = CH2Ph (L-phe)
123

Dipeptides with 3-(trimethylstannyl)alanine building blocks
731
The stannylated dipeptides 3 show the chemical behav-
ior typical for compounds with this substitution pattern.
The dipeptides 3a and 3b were studied in more detail. The
alkyl groups at tin atom can be substituted by halogen
atoms by reaction either with Me3SnCl without a solvent at
60 °C to give 4 or with bromine resulting in 5 (Scheme 2).
No reaction occurred when 3a was treated with HCl in
diethyl ether at room temperature—the starting material
was recovered.
with one donor group of the dipeptide. If one donor group is
intramolecularly coordinated in 4a (and 4b) as a conse-
quence of the asymmetry of the molecule the protons of the
tin-bonded methyl groups should absorb at different fre-
quencies in the 1H spectra. Indeed, in the 1H spectrum of 4a
(and 4b) in CDCl3 two sharp signals appear for the methyl
groups at the tin atom, which are flanked by tin satellites.
This splitting of Sn-methyl signal refers to coordination-
induced configuration stability of the tin atom. Such con-
figuration stabilization is very well documented [30, 31]
(and references cited in the latter) and was observed by us
for similar compounds [22, 23, 32]. The SnꢀꢀꢀC=O coordi-
nation was also reflected in the IR spectra. One of the three
C=O signals of 4a (and 4b) is bathochromically shifted by
nearly 20 cm-1 compared with corresponding signals in 3a
(and 3b). On the basis of our research of SnꢀꢀꢀO=C coor-
dination in comparable systems [21–23], this shift could be
allocated to a relation between the Lewis acid tin atom and
intramolecularly coordinated amide C=O, while the ester
C=O and the carbamide C=O rest unchanged. The preferred
interaction of a monohalogenated tin atom with the C=O
function of an amide group was clearly demonstrated by us
by crystal structure analysis of 3-(diphenylchlorostannyl)-
N-acetylalanine ethyl ester [21].
In all tin compounds containing electronegative sub-
stituents at the metal atom—like 4 and 5—the tin has a
strong tendency to coordinate with donor groups. Which
interactions can be expected between the Lewis acid tin
atom in 4 and 5 and the functional groups existing in the
dipeptides? The three C=O groups of these molecules
should be of different donor ability and on the other hand
there would be a five-membered ring in case of coordina-
tion to the ester C=O group and a six-membered ring in
case of coordination to the amide C=O group. The also
imaginable intramolecular coordination between the tin
atom and the carbamide C=O would give an instable nine-
membered ring—a coordination that is rather improbable.
The association behavior of tin atom with functional
groups may be readily observed by 119Sn NMR because the
coordination number of the tin atom increases on associa-
tion. The spectroscopic data are summarized in the
‘‘Experimental’’. Both the high field shift of 119Sn signal
The reaction of 3a and 3b with bromine yields the di-
bromostannanes 5a and 5b which are very soluble in
halogenated hydrocarbons. The 119Sn signal of 5 is shifted
to higher field compared with that in Me2SnBr2 (in CCl4: d
119Sn = ?70 ppm, 2J(119SnC1H3) = 66.3 Hz) [28, 29].
This is a clear illustration of increase of the coordination
number at the tin atom of 5. The bathochromic shift of
2
and the increase of J(119SnC1H3) coupling constant of 4
compared with Me3SnCl (in CCl4: d 119Sn = ?164.2 ppm,
2J(119SnC1H3) = 58.1 Hz) [28, 29] refer to pentacoordi-
nated tin as result of intramolecular interactions of this atom
R1
Scheme 2
O
O
HCl
NH
O
O
X
O
Et2O
HN
Cl Sn
O
O
R1
Cl
Sn
O
O
R1
NH
O
O
NH
O
O
O
O
HN
+
Sn
HN
Sn
Cl Sn
3a, 3b
4a, 4b
O
O
R1
NH
O
O
2 Br2
O
2 MeBr
+
HN
Br Sn
Br
5a, 5b
123

732
K. Dolling
General procedure for 3-(trimethylstannyl)dipeptides 3
amide C=O of 5 in comparison with 3 demonstrates the
coordination of amide C=O with the tin atom. Likewise the
ester C=O signal is shifted to higher wavelengths and
overlaps with the signal for the N(H)–C(O)=O group. Also
in the light of earlier results [21–23], IR and NMR data
reveal that tin in 5 is hexacoordinated by intramolecular
coordination of the amide C=O and ester C=O group.
To a stirred mixture of 3-(trimethylstannyl)alanine ester
(3.1 mmol) in 20 cm3 CHCl3 at 0 °C were added the corre-
sponding amount of N-benzoyloxycarbonyl amino acid
dissolved in chloroform and then N,N0-dicyclohexylcarbo-
diimide (DCC, 3.1 mmol) also dissolved in chloroform. The
mixture was stirred for 1 h at 0 °C and then 24 h at room
temperature. The precipitate was filtered off. The filtrate was
extracted with a saturated aqueous solution of NaHCO3 and
then with water. The organic layer was dried over Na2SO4.
The solvent was removed under vacuum and the product was
crystallized by addition of ether and low boiling hydrocarbon
and by cooling. The products given in the ‘‘Experimental’’
were obtained by fractional crystallization.
Conclusions
3-(Trimethylstannyl)alanine esters 1a–1d which have a free
amino group react with N-benzoyloxycarbonyl derivatives of
glycine (R2 = H, 2a), L-alanine (R2 = CH3, 2b), D,L-valine
(R2 = CH(CH3)2, 2c), and L-phenylalanine (R2 = CH2Ph,
2d) to give C-stannylated dipeptides 3a–3j in good yields.
The dipeptides 3 were characterized by elemental analysis,
1H and 119Sn NMR spectroscopy, and IR spectroscopy.
The product of reaction of the racemic b-(trimethylstan-
nyl)alanine esters with derivatives of achiral glycine yield
3a–3d as a racemic mixture also. In the case of dipeptides with
L-alanine (R1 = CH3,3e,3f), D,L-valine(R1 = CH(CH3)2,3g,
3h), and L-phenylalanine (R1 = CH2Ph, 3i, 3j) the products
contain two stereocenters and are mixtures of diastereoiso-
mers. After column chromatography and fractional crystalli-
zation the isomers could be isolated and were characterized
by spectroscopy, but their stereochemistry is not yet finally
determined.
N-(Benzoyloxycarbonyl)glycyl-(3-trimethylstannyl)alanine
methyl ester (3a, C17H26N2O5Sn)
Yield: 76.3 %; m.p.: 101–104 °C; 1H NMR (500 MHz,
CDCl3, 30 °C): d = 0.09 (s, 9H, SnMe3, 2J(119SnC1H)
= 54.7 Hz), 1.19 (m, 2H, SnCH2), 3.70 (s, 3H, COOMe),
3.86 (m, 2H, CCH2N), 4.59–4.71 (m, 1H, CH,
3J(119Sn1H) = 41.4 Hz), 5.12 (s, 2H, OCH2), 5.30 (br s, 1H,
NH), 6.37 (d, 1H, NH), 7.28–7.36 (m, 5H, C6H5) ppm; 119Sn
ꢀ
NMR (CDCl3): d = -0.9 ppm; IR (Nujol): m (CO) = 1,641,
1,673, 1,733 cm-1
.
N-(Benzoyloxycarbonyl)glycyl-(3-trimethylstannyl)alanine
ethyl ester (3b, C18H28N2O5Sn)
Yield: 77.7 %; m.p.: 86–87.5 °C; 1H NMR (200 MHz,
The stannylated dipeptides 3 show the chemical
behavior typical for compounds with this substitution pat-
tern. The dipeptides 3a and 3b were studied in more detail.
The alkyl groups at tin atom can be substituted by halogen
atoms by reaction either with Me3SnCl without a solvent at
60 °C to give 4 or with bromine resulting in 5.
2
CDCl3, 25 °C): d = 0.10 (s, 9H, SnMe3, J(119SnC1H) =
54.7 Hz), 1.26 (m ? t, 5H, SnCH2 ? OCH2CH3), 3.86 (m,
2H, CCH2N), 4.15 (m, 2H, COOCH2), 4.64 (m, 1H, CH,
3J(119Sn1H) = 40.7 Hz), 5.12 (s, 2H, OCH2), 5.30 (br s, 1H,
NH), 6.38 (d, 1H, NH), 7.33-7.36 (m, 5H, C6H5) ppm; 119Sn
ꢀ
NMR (CDCl3): d = -1.14 ppm; IR (KBr): m (CO) = 1,652,
1,689, 1,731 cm-1
.
Experimental
N-(Benzoyloxycarbonyl)glycyl-(3-trimethylstannyl)alanine
benzyl ester (3c, C23H30N2O5Sn)
The amino acids were purchased from Sigma and trans-
formed into their N-benzoyloxycarbonyl derivatives
according to standard Schotten–Baumann procedures [33].
The 3-(triorganostannyl)alanine esters [23] were prepared
from iodomethyl triorganostannane [34] and N-(diphenylm-
ethylene)glycine esters. All operations with tin-containing
compounds were carried out under dry argon. The elemental
microanalyses were determined using an Elemental Analyzer
from Carlo Erba. Melting points were detected with a Kofler
heating table microscope. The IR spectra were recorded with
a Zeiss specord or Mattson 5000 FT-IR spectrometer. All the
NMR spectra were recorded in CDCl3 solution by means of
Bruker AC 80, WP 200, or Varian unity 500 spectrometer.
Chemical shifts (d) are reported in ppm and the coupling
constants (J) are in Hz.
1
Yield: 84.8 %; oil; H NMR (200 MHz, CDCl3, 25 °C):
2
d = 0.05 (s, 9H, SnMe3, J(119SnC1H) = 54.7 Hz), 1.24
(m, 2H, SnCH2), 3.85 (m, 2H, CCH2N), 4.69 (m, 1H, CH,
3J(119Sn1H) = 41.6 Hz), 5.12 (s ? m, 4H, 2 x OCH2),
5.44 (m, 1H, NH), 6.56 (d, 1H, NH), 7.32 (m, 10H,
C6H5) ppm; 119Sn NMR (CDCl3): d = -0.7 ppm.
N-(Benzoyloxycarbonyl)glycyl-(3-trimethylstannyl)alanine
t-butyl ester (3d, C20H32N2O5Sn)
Yield: 78.8 %; m.p.: 87–91 °C; 1H NMR (200 MHz, CDCl3,
25 °C): d = 0.10 (s, 9H, SnMe3, 2J(119SnC1H) = 54.6 Hz),
1.24 (m, 2H, SnCH2), 1.44 (s, 9H, COO-t-Bu), 3.86 (m, 2H,
CCH2N), 4.54 (m, 1H, CH, 3J(119Sn1H) = 46.5 Hz), 5.11 (s,
2H, OCH2), 5.37 (m, 1H, NH), 6.41 (d, 1H, NH), 7.33 (m, 5H,
C6H5) ppm; 119Sn NMR (CDCl3): d = -1.5 ppm.
123

Dipeptides with 3-(trimethylstannyl)alanine building blocks
733
N-(Benzoyloxycarbonyl)-L-alanyl-(3-trimethylstannyl)ala-
nine methyl ester (3e, C18H28N2O5Sn)
4.53 (m, 1H, SnCCH), 5.07 (s, 2H, OCH2), 5.20 (m, 1H, NH),
6.15 (d, 1H, NH), 7.23 (m, 10H, C6H5) ppm; 119Sn NMR
(CDCl3): d = -2.15 ppm.
Yield: 57.2 %; m.p.: 88–91 °C; 1H NMR (500 MHz, CDCl3,
25 °C): d = 0.10 (s, 9H, SnMe3, 2J(119SnC1H) = 54.7 Hz),
1.18 (m, 2H, SnCH2), 1.36 (d, 3H, CCH3), 3.68 (s, 3H,
COOMe), 4.23 (m, 1H, CHMe), 4.60 (m, 1H, CH,
3J(119Sn1H) = 40.6 Hz), 5.10 (s, 2H, OCH2), 5.21 (d, 1H,
NH), 6.50 (d, 1H, NH), 7.33 (m, 5H, C6H5) ppm; 119Sn NMR
(CDCl3): d = -1.39 ppm.
General procedure for 3-(chloro-
dimethylstannyl)dipeptides 4
Compound 3 (1.5 mmol) and 1.7 mmol Me3SnCl were
well mixed and heated to 60 °C for 2 days. Volatile
products were then removed under vacuum. The residue
was treated with ether, the mixture filtered from undis-
solved particles, and crystallized by addition of
hydrocarbons. Recrystallization occurs from diethyl ether/
petroleum benzene (b.p. 60–80 °C, Merck).
N-(Benzoyloxycarbonyl)-L-alanyl-(3-trimethylstannyl)ala-
nine ethyl ester (3f, C19H30N2O5Sn)
1
Yield: 56.5 %; oil; H NMR (200 MHz, CDCl3, 25 °C):
2
d = 0.08 (s, 9H, SnMe3, J(119SnC1H) = 54.7 Hz), 1.22
(m ? t, 5H, SnCH2 ? COOCCH3), 1.34(d, 3H, CCH3), 4.13
(qu, 2H, COOCH2), 4.26 (m, 1H, CHMe), 4.60 (m, 1H, CH),
5.07 (s, 2H, OCH2), 5.55 (m, 1H, NH), 6.75 (d, 1H, NH), 7.29
(m, 5H, C6H5) ppm; 119Sn NMR (CDCl3): d = -1.67 ppm.
N-(Benzoyloxycarbonyl)glycyl-(3-chlorodimethylstan-
nyl)alanine methyl ester (4a, C16H23ClN2O5Sn)
Yield: 81 %; m.p.: 93–99 °C; 1H NMR (500 MHz, CDCl3,
2
30 °C): d = 0.62 (s, 3H, SnMe, J(119SnC1H) = 67.4 Hz),
N-(Benzoyloxycarbonyl)-D,L-valyl-(3-trimethylstannyl)ala-
nine methyl ester (3g, C20H32N2O5Sn)
0.75 (s, 3H, SnMe, 2J(119SnC1H) = 66.9 Hz), 1.79 (d,
2
J = 12.5 Hz, 2H, SnCH2, J(119SnC1H) = 76.5 Hz), 3.81
(s, 3H, COOMe ? m, 2H, CCH2N), 4.34 (m, 1H, CCHN),
Yield: 57.6 %; m.p.: 98–102 °C; 1H NMR (200 MHz, CDCl3,
2
25 °C): d = 0.10 (s, 9H, SnMe3, J(119SnC1H) = 54.6 Hz),
5.14 (s, 2H, OCH2), 5.16 (d, 1H, NH), 7.35 (m, 5H, C6H5),
7.43 (m, 1H, NH) ppm; 119Sn NMR (CDCl3): d = 0.67 ppm;
0.88 (d, J = 6.8 Hz, 3H, CMe), 0.95 (d, J = 6.8 Hz, 3H,
CMe), 1.18 (m, 2H, SnCH2), 2.13–2.29 (m, 1H, CHMe2), 3.68
(s, 3H, COOMe), 4.02 (m, 1H, CH), 4.60 (m, 1H, CH), 5.10 (s,
2H, OCH2), 5.22 (m, 1H, NH), 6.37 (d, 1H, NH), 7.33 (m, 5H,
C6H5) ppm; 119Sn NMR (CDCl3): d = -1.57 ppm.
-1
ꢀ
IR (KBr): m (CO) = 1,628, 1,710, 1,736 cm
.
N-(Benzoyloxycarbonyl)glycyl-(3-chlorodimethylstan-
nyl)alanine ethyl ester (4b, C17H25ClN2O5Sn)
Yield: 78 %; m.p.: 87–93 °C; 1H NMR (500 MHz, CDCl3,
N-(Benzoyloxycarbonyl)-D,L-valyl-(3-trimethylstannyl)ala-
nine ethyl ester (3h, C21H34N2O5Sn)
30 °C): d = 0.62 (s, 3H, SnMe, 2J(119SnC1H) = 69.8 Hz),
2
0.77 (s, 3H, SnMe, J(119SnC1H) = 68.4 Hz), 1.32 (t, 3H,
Yield: 58.3 %; m.p.: 84–88 °C; 1H NMR (500 MHz, CDCl3,
25 °C): d = 0.10 (s, 9H, SnMe3, 2J(119SnC1H) = 54.7 Hz),
0.92 (d, J = 6.8 Hz, 3H, CMe), 0.95 (d, J = 6.8 Hz, 3H,
CMe), 1.18 (m, 2H, SnCH2), 1.25 (t, 3H, COOCMe), 2.07–
2.14 (m, 1H, CHMe2), 3.94 (m, 1H, CH), 4.08–4.21 (qu, 2H,
COOCH2), 4.62 (m, 1H, CH, 3J(119Sn1H) = 40.9 Hz), 5.09
(s, 2H, OCH2), 5.28 (m, 1H, NH), 6.13 (d, 1H, NH), 7.30 (m,
5H, C6H5) ppm; 119Sn NMR (CDCl3): d = -2.26 ppm.
COOCCH3), 1.70 (d, 2H, SnCH2), 3.84 (m, 2H, CCH2N),
4.19–4.30 (m, 1H, CCHN ? qu, 2H, COOCH2C), 5.12 (s,
2H, OCH2), 5.26 (d, 1H, NH), 7.38 (m, 5H, C6H5), 7.53 (m,
1H, NH) ppm; 119Sn NMR (CDCl3): d = 0.3 ppm; IR
-1
ꢀ
(KBr): m (CO) = 1,627, 1,711, 1,732 cm
.
General procedure for 3-(dibromo-
methylstannyl)dipeptides 5
N-(Benzoyloxycarbonyl)-L-phenylalanyl-(3-trimethylstan-
nyl)alanine methyl ester (3i, C24H32N2O5Sn)
To a stirred solution of 3 (2 mmol) in 15 cm3 chloroform at
-30 °C was added dropwise a solution of 0.64 g bromine
(4 mmol) in chloroform. After 1 h stirring at room tem-
perature the solvent was removed under vacuum. The
residue was crystallized from diethyl ether/petroleum
benzene (b.p. 60–80 °C, Merck).
Yield: 67.8 %; m.p.: 104–108 °C; 1H NMR (200 MHz,
2
CDCl3, 25 °C): d = 0.06 (s, 9H, SnMe3, J(119SnC1H) =
54.7 Hz), 1.01 (m, 2H, SnCH2), 3.06 (d, 2H, CCH2), 3.66 (s,
3H, COOMe), 4.40 (m, 1H, CCHN), 4.55 (m, 1H, SnCCH),
5.06 (s, 2H, OCH2), 5.20 (m, 1H, NH), 6.20 (d, 1H, NH), 7.23
(m, 10H, C6H5) ppm; 119Sn NMR (CDCl3): d = -1.96 ppm.
N-(Benzoyloxycarbonyl)glycyl-(3-dibromo-
methylstannyl)alanine methyl ester
N-(Benzoyloxycarbonyl)-L-phenylalanyl-(3-trimethylstan-
nyl)alanine ethyl ester (3j, C25H34N2O5Sn)
(5a, C15H20Br2N2O5Sn)
Yield: 64.5 %; m.p.: 63–68 °C; 1H NMR (200 MHz, CDCl3,
25 °C): d = 0.07 (s, 9H, SnMe3, 2J(119SnC1H) = 54.7 Hz),
1.02 (m, 2H, SnCH2), 1.23 (t, 3H, COOCCH3), 3.06 (d, 2H,
CCH2), 4.07 (m, 2H, COOCH2C), 4.39 (m, 1H, CCH2Ph),
Yield: 58 %; m.p.: 38–41 °C; 1H NMR (500 MHz, CDCl3,
30 °C): d = 1.47 (s, 3H, MeSn, 2J(119SnC1H) = 97.1 Hz),
2.02 (m, 2H, SnCH2), 3.82 (s, 3H, COOMe), 3.87 (m, 2H,
CCH2), 4.49 (m, 1H, CCHN), 5.14 (s, 2H, OCH2), 5.24 (m,
123

734
K. Dolling
11. Nath M, Pokharia S, Eng G, Song X, Kumar A, Gielen M,
Willem R, Biesemans M (2004) Appl Organomet Chem 18:460
12. Nath M, Singh H, Kumar P, Kumar A, Song X, Eng G (2009)
Appl Organomet Chem 23:347
1H, NH), 7.26 (m, 5H, C6H5), 7.59 (m, 1H, NH) ppm;
119
ꢀ
Sn NMR (CDCl3): d = -139.6 ppm; IR (KBr): m
(CO) = 1,620, 1,706 cm-1
.
13. Baul TSB (2008) Appl Organomet Chem 22:195
14. Nath M (2008) Appl Organomet Chem 22:598
15. Nath M, Singh H, Eng G, Song X (2008) Spectrochim Acta A
71:529
16. Nath M, Pokharia S, Eng G, Song X, Kumar A (2004) Synth
React Inorg Met-Org Chem 34:1689
17. Klein J, Lebelt I, Borsdorf R (1996) J Prakt Chem 338:544
18. Sandhu GK, Kaur G (1990) J Organomet Chem 388:63
19. Deska J, Kazmaier U (2007) Angew Chem Int Ed 46:4570
20. Wilbur DS, Hamlin DK, Srivastava RR, Burns HD (1993) Bio-
conjug Chem 4:574
N-(Benzoyloxycarbonyl)glycyl-(3-dibromomethylstan-
nyl)alanine ethyl ester (5b, C16H22Br2N2O5Sn)
Yield: 53 %; 1H NMR (500 MHz, CDCl3, 30 °C): d = 1.31 (t,
3H, COOCMe), 1.47 (s, 3H, MeSn, 2J(119SnC1H) = 96.4 Hz),
1.92 (m, 2H, SnCH2), 3.87 (m, 2H, CCH2), 4.27 (qu, 2H,
COOCH2C), 4.48 (m, 1H, CCHN), 5.14 (s, 2H, OCH2), 5.20
(m, 1H, NH), 7.18 (m, 5H, C6H5), 7.44 (m, 1H, NH) ppm; 119Sn
ꢀ
NMR (CDCl3): d = -141.7 ppm; IR (KBr): m (CO) = 1,621,
1,708 cm-1
.
¨
21. Dolling K, Hartung H, Schollmeyer D, Weichmann H (1991) Z
Anorg Allg Chem 600:153
¨
22. Dolling K, Krug A, Hartung H, Weichmann H (1995) Z Anorg
Allg Chem 621:63
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