A novel approach to the synthesis of amino acids based on cobalt bis(dicarbollide)

Article abstract of DOI:10.1007/s11172-010-0392-9

A novel approach to the synthesis of boron-containing amino acids based on ring opening of cyclic oxonium derivatives of polyhedral boron hydrides under the action of the terminal functional groups of natural amino acids was proposed. This approach was su

Full text of DOI:10.1007/s11172-010-0392-9

Russian Chemical Bulletin, International Edition, Vol. 59, No. 12, pp. 2302—2308, December, 2010
2302
A novel approach to the synthesis of amino acids based
on cobalt bis(dicarbollide)
I. A. Lobanova, M. Ya. Berzina, I. B. Sivaev, P. V. Petrovskii, and V. I. Bregadze
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation
Eꢀmail: sivaev@ineos.ac.ru
A novel approach to the synthesis of boronꢀcontaining amino acids based on ring opening of
cyclic oxonium derivatives of polyhedral boron hydrides under the action of the terminal
functional groups of natural amino acids was proposed. This approach was successfully impleꢀ
mented for the synthesis of cobalt bis(dicarbollide) — tyrosine conjugate.
Key words: cobalt complexes, carboranes, oxonium compounds, amino acids, tyrosine,
boron neutron capture therapy of cancer.
Boron neutron capture therapy (BNCT) of cancer is
tophan, histidine, valine, leucine, and isoleucine) through
the BBB.7—9 It has been shown that a number of clinically
used drugs — mimetics of tyrosine (levodopa, thyroxine,
triiodothyroxine, melphalan),9—11 as well as some comꢀ
pounds being potential diagnostic or therapeutic agents
(Oꢀ6ꢀ18Fꢀfluoroꢀ3ꢀmethyllevodopa,12 2ꢀaminoꢀ3ꢀ{4ꢀ[2ꢀ
(3ꢀbenzoylphenyl)propionyloxy]phenyl}propionic acid13)
can penetrate through the BBB with the aid of the aminoꢀ
acid transporter LAT1. In the present work, we describe
the synthesis of boronꢀcontaining derivatives of tyrosine
that contain the cobalt bis(dicarbollide) fragment in the
side chain.
a binary method for cancer treatment, wherein the reacꢀ
tion of two components that are virtually harmless for
health affords highly toxic products damaging the cancer
cell. The method is based on selective accumulation of the
nonꢀradioactive 10B isotopes in the cancer cells followed
by their treatment with a flux of thermal neutrons. The
irradiation results in the formation of highꢀenergy fission
products having short freeꢀpath lengths comparable with
the cell size, which allows selective destruction of tumor
cells with the surrounding healthy tissue being virtually
nonaffected.1—3
One of the main requirements for BNCT is the availꢀ
ability of the boronꢀcontaining medicines that can be acꢀ
cumulated selectively in the tumor tissue at the concenꢀ
trations sufficient for the intracellular nuclear reaction to
proceed (20—35 μg of 10B per 1 g of tumor). In particular,
amino acids, peptides, and nucleotides can be used as
molecules carrying out the targeted delivery of boron to
a tumor.
Since BNCT is a complex set of activities associated
with the use of neutron beam from a nuclear reactor, this
therapy is applied for treatment of the tumors that cannot
be treated using conventional procedures, primarly, for
treatment of highlyꢀmalignant brain gliomas.4 In this conꢀ
nection, an additional prerequisite for selective delivery of
boronꢀcontaining drugs is its penetration through the
bloodꢀbrain barrier (BBB).5 One of the possible ways for
overcoming the BBB is the use of membrane transport
systems located in the plasma membrane.6 The aminoꢀ
acid transporter LAT1 (large neutral amino acid transꢀ
porter 1) is an example of such systems, which are capable
of transferring efficiently Lꢀamino acids with the aromatic
or branched side chain (tyrosine, phenylalanine, trypꢀ
Results and Discussion
Owing to the combination of high chemical stability,
low toxicity, good water solubility (in the form of sodium
salts), and sufficiently high lipophilicity, cobalt bisꢀ
(dicarbollide) [3,3´ꢀCo(1,2ꢀC2B9H11)2]– derivatives14
attract ever increasing attention as a basis for the design
of medicines for BNCT. Earlier,15 we have proposed
a method for functionalization of cobalt bis(dicarbꢀ
ollide) by opening of its cyclic oxonium derivative
[8ꢀО(CH2CH2)2Oꢀ3,3´ꢀCo(1,2ꢀC2B9H10)(1´,2´ꢀC2B9H11)]
(1), which has become over the past years a classical methꢀ
od for the preparation of its organic and bioorganic derivꢀ
atives.16
This approach has been used earlier for the preparation
of the first amino acid based on cobalt bis(dicarbollide) by
Sorenson´s method by opening of the oxonium ring of
compound 1 with diethyl acetamidomalonate.15 In the
present work, we decided to use the phenolic group of
tyrosine for opening of the oxonium ring. The tyrosine
molecule has three nucleophilic reaction sites: phenolic,
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2246—2251, December, 2010.
1066ꢀ5285/10/5912ꢀ2302 © 2010 Springer Science+Business Media, Inc.

Cobalt bis(dicarbollide)ꢀconjugated tyrosine
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 12, December, 2010
2303
1
amino, and carboxylic groups. Opening of cyclic oxonium
derivatives of polyhedral boron hydrides under the action
of the phenolate anion and amines is well known16 and
a few examples of opening of the oxonium ring of comꢀ
pound 1 under the action of the carboxylate anion have
been described.17 Selective opening of the oxonium ring
requires the use of protective groups, the protection of
amino group being obligatory, since cyclic oxonium deꢀ
rivatives react with the amino groups of the amino acid
esters in the absence of bases.16a However, we have found
earlier that the reaction of compound 1 with pꢀhydroxyꢀ
benzoic acid in the presence of K2CO3 in acetonitrile proꢀ
ceeds selectively at the hydroxyl group.18 Therefore, we
first studied the reaction of compound 1 with NꢀBocꢀLꢀ
tyrosine. We found that the reaction in acetonitrile in the
presence of K2CO3 proceeds selectively to form ester 2,
i.e., the dioxane ringꢀopening product, under the action of
the carboxylate anion (Scheme 1).
The structure of compound 2 was established by H
and 13C NMR spectroscopy and mass spectrometry. The
1H NMR spectrum of compound 2 contains the signals
for the protons of the CH groups of cobalt bis(dicarbollide)
at δ 4.13 and 4.09, the signals for the aromatic ring at
δ 7.06 and 6.75, the signals for the methylene protons of
tyrosine in the region of δ 3.06—2.86, the signal for the
CH group of tyrosine at δ 4.35, and the signal for the tertꢀ
butyl group at δ 1.35. The signals for the open dioxane ring
appear as a set of multiplets in the region of δ 4.23—3.56.
The downfield shift of one of the signals for the opened
dioxane ring (the signal at δ 4.23) evidences the ester
formation. The 13C NMR spectrum displays a signal
at δ 172.6, which corresponds to the carbonyl of the
ester group.
An additional confirmation of the structure of comꢀ
pound 2 is its acid hydrolysis to the corresponding alcohol
3, whose synthesis has been described earlier.15
Scheme 1

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Russ.Chem.Bull., Int.Ed., Vol. 59, No. 12, December, 2010
Lobanova et al.
Thus, the protection of the carboxyl group was the
prerequisite for opening of the oxonium ring with the pheꢀ
nolate anion of tyrosine.19 Indeed, the reaction of comꢀ
pound 1 with the ethyl ester of NꢀtrifluoroacetylꢀLꢀtyꢀ
rosine in acetonitrile in the presence of K2CO3 affords the
target product 4 in high yield (Scheme 2).
acetonitrile in the presence of K2CO3 affords the protectꢀ
ed boronꢀcontaining tyrosine 5 (Scheme 3). The 1H NMR
spectrum of compound 5 contains the signals for the proꢀ
tons of the aromatic ring in the region of δ 7.1—6.9,
the protons of the methylene group in the region of
δ3.14—3.03 and the CH and CH2 groups of oxazolidinꢀ5ꢀ
one at δ 5.26 and 4.45, and the protons of the tertꢀbutyl
group at δ 1.51, as well as the signal for the protons of the
CH groups of the cobalt bis(dicarbollide) fragment at δ 4.26
and the signals for the protons of the open dioxane ring in
the region of δ 4.13—3.59. The IR spectrum of comꢀ
pound 5 contains the bands typical of oxazolidinꢀ5ꢀone at
1
The H NMR spectrum of compound 4 contains the
signals for the protons of the aromatic ring at δ 7.16 and
6.87, the protons of the methylene group of tyrosine in the
region of δ 3.22—2.98, the CH group of tyrosine at δ 4.66,
and the ethyl group at δ 4.13 and 1.18, as well as the signal
for the protons of the CH groups of cobalt bis(dicarbollide)
at δ 4.20 and the signals for the protons of the open diꢀ
oxane ring in the region of δ 4.08—3.56. The 13C NMR
spectrum contains the signals for the carbon atoms of the
trifluoroacetyl group as quartets at δ156.6 (JC,F = 37 Hz)
and 116.0 (JC,F = 287 Hz). Unfortunately, all our atꢀ
tempts to remove the protecting groups under mild condiꢀ
tions were unsuccessful and the use of drastic conditions
(longꢀterm boiling with hydrochloric acid in ethanol) reꢀ
sults in decomposition of the metallocarborane skeleton.
In the search for the tyrosine derivatives with easily
removable protecting groups, we prepared (4S)ꢀ3ꢀtertꢀbutꢀ
oxycarbonylꢀ4ꢀ(4ꢀhydroxybenzyl)ꢀ5ꢀoxazolidinone by the
reaction of NꢀBocꢀLꢀtyrosine with paraformaldehyde in
the presence of pꢀtoluenesulfonic acid by analogy with the
derivative of Lꢀ4ꢀiodophenylalanine described earlier.20
The reaction of the oxazolidinone with compound 1 in
1802 cm–1 and the tertꢀbutoxy group at 1716 cm–1
.
The treatment of compound 5 with a solution of NaOH
in aqueous ethanol at room temperature results in the hyꢀ
drolysis of the aminalꢀacetal fragment to form salt 6 (see
Scheme 3). In the 1H NMR spectrum of compound 6, the
signal for the CH2 group of the oxazolidinꢀ5ꢀone ring disꢀ
appears, and the disappearance of the characteristic
band of oxazolidinꢀ5ꢀone at 1802 cm–1 and the appearꢀ
ance of the band of carboxylate anion at 1697 cm–1 are
observed in the IR spectrum. Subsequent treatment of
compound 6 with a solution of HCl in ethanol results in
the removal of the Boc group to form the boronꢀcontainꢀ
ing tyrosine 7 isolated in the neutral Nꢀprotonated form
(see Scheme 3).
The approach described above can be used for the prepꢀ
aration of boronꢀcontaining derivatives of other amino
Scheme 2

Cobalt bis(dicarbollide)ꢀconjugated tyrosine
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 12, December, 2010
2305
Scheme 3
acids having the terminal functional groups that can act as
nucleophiles (serine, cysteine, lysine, etc.).
Experimental
The reaction of the dioxane derivative 1 with NꢀBoсꢀ
Lꢀserine and ethyl ester of NꢀBocꢀLꢀserine in acetonitirle
in the presence of K2CO3 results in opening of the oxoniꢀ
um ring under the action of carboxyl or alkoxyl groups to
form compounds 8 and 9, respectively (Scheme 4). At the
same time, the lower acidity of the alcoholic hydroxy group
compared to the phenolic one is the cause of lower yield of
the target product 9, which requires further optimization
of the synthesis conditions.
Thus, we proposed a novel approach to the synthesis of
boronꢀcontaining amino acids, which is based on the ring
opening of the cyclic oxonium derivatives of polyhedral
boron hydrides under the action of the terminal functional
groups of natural amino acids.
1
H, 11B, 11B{1H}, and 13C NMR spectra were recorded on
Bruker Avance 400 and Bruker Avance 600 spectrometers. Negꢀ
ativeꢀion electrospray ionization (ESI) mass spectra were reꢀ
corded on a micrOTOF Q II (Bruker Daltonics) instrument.
The course of reactions was monitored by TLC on Kieselgel 60
F245 (Merck) plates. Acetonitrile was dried by distillation
over P2O5 and CaH2. The dioxane derivative 1, ethyl ester of
NꢀtrifluoroacetylꢀLꢀtyrosine, and ethyl ester of NꢀBocꢀLꢀserine
were prepared according to the previously published proceꢀ
dures.21,19,22
(4S)ꢀ3ꢀtertꢀButoxycarbonylꢀ4ꢀ(4ꢀhydroxybenzyl)ꢀ1,3ꢀoxazolꢀ
idinꢀ5ꢀone.
20.0 mmol), paraformaldehyde (3.00 g, 100.0 mmol), and
TsOH•H2O (0.38 g, 2.0 mmol) in toluene (250 mL) was reꢀ
fluxed with vigorous stirring for 4 h with azeotropic distillation of
A suspension of NꢀBocꢀLꢀtyrosine (5.62 g,

2306
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 12, December, 2010
Lobanova et al.
Scheme 4
water. The reaction mixture was cooled to room temperature
and filtered. The filtrate was washed with 1 M NaHCO3, dried
with Na2SO4, and concentrated to dryness on a rotary evaporaꢀ
tor to yield the white product (3.99 g, 68%). 1H NMR (CDCl3),
δ: 7.00 (d, 2 H); 6.74 (d, 2 H); 5.20 (d, 1 H); 4.44 (s, 1 H); 4.29
(d, 1 H); 3.28 (d, 1 H); 3.08 (d, 1 H); 1.51 (s, 9 H). 13C NMR
(CDCl3), δ: 172.2, 155.7, 151.8, 130.8, 126.1, 115.7, 82.4, 78.2,
56.7, 34.9, 28.3.
Dipotassium {2ꢀ[2ꢀ(uncosahydroꢀ1´,1″,2´,2″ꢀtetracarbaꢀ3´ꢀ
commoꢀcobaltaꢀclosoꢀtricosaboratoꢀ8´ꢀoxy)ethoxy]ethyl}[Nꢀ
(tertꢀbutoxycarbonyl)ꢀLꢀtyrosinate] (2). To a solution of NꢀBocꢀ
Lꢀtyrosine (0.24 g, 0.85 mmol) in MeCN (15 mL), compound 1
(0.35 g, 0.85 mmol) and K2CO3 (1.17 g, 8.5 mmol) were added.
The reaction mixture was refluxed for 1 h and then cooled to
room temperature. The excess of K2CO3 was filtered off and the
solvent was removed on a rotary evaporator to yield the orange
oily product (0.60 g, 96%). 1H NMR (acetoneꢀd6), δ: 7.06 (d, 2 H,
J = 8.4 Hz); 6.75 (d, 2 H, J = 8.4 Hz); 6.18 (d, 1 H, NH,
J = 7.6 Hz); 4.35 (m, 1 H); 4.23 (m, 2 H); 4.13 (s, 2 H, CHcarb);
4.09 (s, 2 H, CHcarb); 3.67 (m, 4 H); 3.56 (m, 2 H); 3.06—2.86
(m, 2 H); 1.35 (s, 9 H). 13C{1H} NMR (acetoneꢀd6), δ: 172.6,
156.7, 155.9, 130.3, 126.9, 115.4, 79.4, 72.2, 68.7, 68.5, 64.3,
55.5, 52.5, 46.7, 36.3, 28.0. 11B NMR (acetoneꢀd6,), δ: 23.3 (s, 1 B);
4.6 (d, 1 B); 0.4 (d, 1 B); –2.5 (d, 1 B); –4.46 (d, 2 B); –7.7
(d, 6 B); –17.3 (d, 2 B); –20.4 (d, 2 B); –22.0 (d, 1 B); –28.4
(d, 1 B). MS (ESI), m/z: 690 [М]–.
compound 1 (0.13 g, 0.32 mmol) and K2CO3 (0.44 g, 3.20 mmol)
were added. The reaction mixture was heated for 2.5 h to 60 °C
and then cooled to room temperature. The excess of K2CO3 was
filtered off, the solvent was removed on a rotary evaporator, and
the resulted residue was chromatorgraphed on a silica gel colꢀ
umn (the eluent was MeCN : CH2Cl2 (1 : 4)) to yield the orange
oily product (0.21 g, 89%). 1H NMR (acetoneꢀd6), δ: 8.69
(d, 1 H, J = 8.0 Hz); 7.16 (d, 2 H, J = 8.6 Hz); 6.87 (d, 2 H,
J = 8.6 Hz); 4.66 (m, 1 H); 4.20 (s, 4 H, CHcarb); 4.13 (q, 2 H,
J =7.2 Hz); 4.08 (t, 2 H, J = 4.8 Hz); 3.78 (t, 2 H, J = 4.8 Hz);
3.62 (m, 2 H); 3.56 (m, 2 H); 3.22—2.98 (m, 2 H); 1.18 (t, 3 H,
J = 7.2 Hz). 13C{1H} NMR (acetoneꢀd6), δ: 169.9, 158.1, 156.6
(JC,F = 37 Hz); 130.2, 128.5, 114.4, 116.0 (JC,F = 287 Hz); 72.0,
69.3, 68.4, 67.5, 61.3, 54.5, 54.0, 46.5, 35.6, 13.5. 11B{1H} NMR
(acetoneꢀd6,), δ: 23.2 (s, 1 B); 4.3 (d, 1 B); 0.4 (d, 1 B); –2.5 (d, 1 B);
–4.4 (d, 2 B); –8.0 (d, 6 B); –17.3 (d, 2 B); –20.4 (d, 2 B); –21.8
(d, 1 B); –28.5 (d, 1 B).
Cesium salt of (4S)ꢀ3ꢀtertꢀbutoxycarbonylꢀ4ꢀ(4ꢀ{2ꢀ[2ꢀ(unꢀ
cosahydroꢀ1´,1″,2´,2″ꢀtetracarbaꢀ3´ꢀcommoꢀcobaltaꢀclosoꢀtriꢀ
cosaboratoꢀ8´ꢀoxy)ethoxy]ethoxy}benzyl)ꢀ1,3ꢀoxazolidinꢀ5ꢀone
(5). To a solution of compound 1 (0.30 g, 0.73 mmol) in MeCN
(10 mL), (4S)ꢀ3ꢀtertꢀbutoxycarbonylꢀ4ꢀ(4ꢀhydroxybenzyl)ꢀ1,3ꢀ
oxazolidinꢀ5ꢀone (0.21 g, 0.78 mmol) and K2CO3 (1.08 g,
7.80 mmol) were added. The reaction mixture was stirred for
22 h at room temperature. The excess of K2CO3 was filtered off
and the solvent was removed on a rotary evaporator. The reꢀ
sulted residue was dissolved in acetone and an excess of an aqueꢀ
ous solution of CsCl was added. The formed oily precipitate
was chromatographed on a silica gel column (the eluent was
CH2Cl2 : CH3CN (10 : 1)) to obtain the orange product (0.51 g,
Potassium ethyl Oꢀ{2ꢀ[2ꢀ(uncosahydroꢀ1´,1″,2´,2″ꢀtetracarbaꢀ
3´ꢀcommoꢀcobaltaꢀclosoꢀtricosaboratoꢀ8´ꢀoxy)ethoxy]ethyl}ꢀNꢀ
trifluoroacetylꢀLꢀtyrosinate (4). To a solution of ethyl ester of
NꢀtrifluoroacetylꢀLꢀtyrosine (0.10 g, 0.32 mmol) in MeCN (15 mL),

Cobalt bis(dicarbollide)ꢀconjugated tyrosine
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 12, December, 2010
2307
94%). 1H NMR (acetoneꢀd6), δ: 7.1—6.9 (m, 4 H); 5.26 (m, 1 H);
4.45 (m, 2 H); 4.26 (s, 4 H, CHcarb); 4.13 (t, 2 H, J = 5.0 Hz);
3.82 (t, 2 H, J = 5.0 Hz); 3.64 (t, 2 H, J = 5.0 Hz); 3.59 (t, 2 H,
J = 5.0 Hz); 3.44—3.19 (m, 1 H); 3.03 (d, 1 H, J = 14 Hz); 1.51
(s, 9 H). 11B NMR (acetoneꢀd6), δ: 23.3 (s, 1 B); 4.6 (d, 1 B); 0.5
(d, 1 B); –2.5 (d, 1 B); –4.4 (d, 2 B); –7.2 (d, 6 B); –17.3
(d, 2 B); –20.4 (d, 2 B); –22.0 (d, 1 B); –28.4 (d, 1 B). 13C{1H}
NMR (acetoneꢀd6), δ: 172.2, 158.1, 151.6, 130.8, 127.6, 114.7,
81.0, 77.9, 72.2, 69.3, 68.4, 67.5, 56.3, 53.2, 46.5, 35.2, 27.6. IR,
ν/cm–1: 2552, 1802, 1716.
Dicesium Nꢀ(tertꢀbutoxycarbonyl)ꢀOꢀ{2ꢀ[2ꢀ(uncosahydroꢀ
1´,1″,2´,2″ꢀtetracarbaꢀ3´ꢀcommoꢀcobaltaꢀclosoꢀtricosaboratoꢀ
8´ꢀoxy)ethoxy]ethoxy}ꢀLꢀtyrosinate (6). To a solution of comꢀ
pound 5 (0.16 g, 0.20 mmol) in MeOH (10 mL), a 2 М aqueous
solution of NaOH was added. The reaction mixture was stirred
for 1 h at room temperature and then acetone (40 mL) was
added. The organic layer was separated. The procedure was reꢀ
peated twice. The organic phases were combined, concentrated
to 10 mL on a rotary evaporator, and then treated with an excess
of an aqueous solution of CsCl. The formed orange precipitate
was filtered off and dried to yield the product (0.13 g, 86%).
1H NMR (acetoneꢀd6), δ: 7.17 (d, 2 H, J = 8.3 Hz); 6.84 (d, 2 H,
J = 8.3 Hz); 6.08—5.94 (m, 1 H); 4.22 (s, 4 H, CHcarb); 4.09
(t, 2 H, J = 4.6 Hz); 3.80 (t, 2 H, J = 4.6 Hz); 3.68 (t, 2 H,
J = 4.6 Hz); 3.60 (t, 2 H, J = 4.6 Hz); 3.22—3.12 (m, 2 H); 1.40
(s, 9 H). 11B NMR (acetoneꢀd6), δ: 23.4 (s, 1 B); 4.9 (d, 1 B); 0.5
(d, 1 B); –2.4 (d, 1 B); –4.4 (d, 2 B); –7.1 (d, 6 B); –17.1
(d, 2 B); –20.3 (d, 3 B); –28.5 (d, 1 B). IR, ν/cm–1: 2547 (νBH);
1715 (νC=O); 1697 (νC=O).
Cesium ethylꢀNꢀ(tertꢀbutoxycarbonyl)ꢀOꢀ{2ꢀ[2ꢀ(uncosahydroꢀ
1´,1″,2´,2″ꢀtetracarbaꢀ3´ꢀcommoꢀcobaltaꢀclosoꢀtricosaboratoꢀ
8´ꢀoxy)ethoxy]ethyl}ꢀLꢀserinate (9). To a solution of ethyl ester
of NꢀBocꢀLꢀserine (0.18 g, 0.79 mmol) in MeCN (5 mL), comꢀ
pound 1 (0.33 g, 0.79 mmol) and K2CO3 (1.09 g, 7.90 mmol)
were added. The reaction mixtrure was refluxed for 4 h and
cooled to room temperature, the excess of K2CO3 was filtered
off, and the solvent was removed on a rotary evaporator. The
resulted residue was dissolved in acetone and treated with an
excess of an aqueous solution of CsCl. The formed precipitate
was chromatographed on a silica gel column using a mixture of
MeCN and CH2Cl2 as an eluent to yield the product (0.10 g,
18.6%). 1H NMR (acetoneꢀd6), δ: 8.69 (d, 1 H, J = 8.0 Hz); 7.16
(d, 2 H, J = 8.6 Hz); 6.87 (d, 2 H, J = 8.6 Hz); 4.66 (m, 1 H);
4.20 (s, 4 H, CHcarb); 4.13 (q, 2 H, J = 7.2 Hz); 4.08 (t, 2 H,
J = 4.8 Hz); 3.78 (t, 2 H, J = 4.8 Hz); 3.62 (m, 2 H); 3.56 (m, 2 H);
3.22—2.98 (m, 2 H); 1.18 (t, 3 H, J = 7.2 Hz). 11B NMR (aceꢀ
toneꢀd6), δ: 23.2 (s, 1 B); 4.3 (d, 1 B); 0.4 (d, 1 B); –2.5 (d, 1 B);
–4.4 (d, 2 B); –8.0 (m, 6 B); –17.3 (d, 2 B); –20.4 (d, 2 B);
–21.8 (d, 1 B); –28.5 (d, 1 B).
This work was financially supported by the Russian
Foundation for Basic Research (Projects Nos 08ꢀ03ꢀ00463,
09ꢀ03ꢀ00701, and 10ꢀ03ꢀ00698) and the Presidium of the
Russian Academy of Sciences (Program "Development of
methods for the preparation of chemical substances and
design of new materials").
References
(4S)ꢀ8´ꢀ(2ꢀ{2ꢀ[4ꢀ(2ꢀAmmonioꢀ2ꢀcarboxyethyl)phenoxy]ꢀ
ethoxy}ethoxy)uncosahydroꢀ1´,1″,2´,2″ꢀtetracarbaꢀ3´ꢀcommoꢀ
cobaltaꢀclosoꢀtricosaborate (7). To a solution of compound 6
(0.21 g, 0.31 mmol) in EtOH (8 mL), SOCl2 (1 mL) was added
dropwise The reaction mixture was stirred at room temperature
for 27 h and concentrated to dryness on a rotary evaporator to
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1
yield the orange product (0.11 g, 70%). H NMR (acetoneꢀd6),
δ: 7.5 (d, 2 H, J = 8.6 Hz); 6.97 (d, 2 H, J = 8.6 Hz); 5.38 (m, 1 H);
4.31 (s+t, 6 H); 4.14 (t, 2 H, J = 4.8 Hz); 3.81 (t, 2 H, J = 4.8 Hz);
3.58 (m, 2 H); 3.53—3.15 (m, 2 H). 11B NMR (acetoneꢀd6), δ:
22.8 (C, 1 B); 3.8 (d, 1 B); 0.3 (d, 1 B); –2.4 (d, 1 B); –4.2 (d, 2 B);
–7.4 (d, 2 B); –8.3 (d, 4 B); –17.3 (d, 2 B); –20.4 (d, 2 B); –22.0
(d, 1 B); –28.4 (d, 1 B). IR, ν/cm–1: 2558 (νBH), 1747 (νC=O),
1726 (νC=O).
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Potassium {2ꢀ[2ꢀ(uncosahydroꢀ1´,1″,2´,2″ꢀtetracarbaꢀ3´ꢀ
commoꢀcobaltaꢀclosoꢀtricosaboratoꢀ8´ꢀoxy)ethoxy]ethyl}[Nꢀ
(tertꢀbutoxycarbonyl)ꢀLꢀserinate] (8). To a solution of NꢀBocꢀLꢀ
serine (0.14 g, 0.64 mmol) in MeCN (10 mL), compound 1 (0.26 g,
0.64 mmol) and K2CO3 (0.88 g, 6.40 mmol) were added. The
reaction mixture was refluxed for 1 h and then cooled to room
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was removed on a rotary evaporator. The resulted residue
was chromatographed on a silica gel column (the eluent was
MeCN : CH2Cl2 (1 : 5)) to yield the orange oily product (0.40 g,
94%). 1H NMR (acetoneꢀd6), δ: 6.16 (d, 1 H, J = 7.6 Hz); 4.39—4.21
(m, 2 H); 4.21—4.02 (m, 1 H); 4.15 (s, 2 H, CHcarb); 4.11 (s, 2 H,
CHcarb); 3.95—3.78 (m, 2 H); 3.70 (t, 2 H, J = 4.6 Hz); 3.65
(m, 2 H); 3.55 (m, 2 H); 1.40 (s, 9 H). 13C NMR (acetoneꢀd6), δ:
171.0, 155.6, 78.8, 71.9, 68.7, 68.4, 64.2, 62.3, 56.0, 53.7, 46.5,
27.7. 11B NMR (acetoneꢀd6), δ: 23.2 (s, 1 B); 4.4 (d, 1 B); 0.4 (d, 1 B);
–2.6 (d, 1 B); –4.5 (d, 2 B); –7.7 (d, 4 B); –17.3 (d, 2 B); –20.4
(d, 2 B); –22.1 (d, 1 B); –28.6 (d, 1 B). MS (ESI), m/z: 614 [М]–.
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Received November 1, 2010