Synthesis of a glycosylated ortho-carboranyl amino acid

Article abstract of DOI:10.1055/s-2003-40834

The preparation of an ortho-carborane derivative bearing both carbohydrate and amino acid substituents is presented; opening of a glucofuranuro-γ-lactone derivative with propargylamines, cycloaddition of decaborane to an acetylenic bond and amidation with a N-Fmoc-glutamate derivative are the key-steps in this synthesis.

Full text of DOI:10.1055/s-2003-40834

LETTER
1399
Synthesis of a Glycosylated ortho-Carboranyl Amino Acid
Synthesisof
a
Glh
iborany
s
l
Amino A
t
cid ian Thimon,a,b Luigi Panza,b Christophe Morin*a
a
Laboratoire d’Etudes Dynamiques et Structurales de la Sélectivité (associé au CNRS, UMR 5616), Départment de Chimie, Université
Joseph Fourier, B.P. 53-X, 38041 Grenoble, France
Fax +33(476)514927; E-mail: christophe.morin@ujf-grenoble.fr
b
Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, Viale Ferrucci 33,
28100 Novara, Italy
Received 24 May 2003
The carborane derivative shown in Figure 1 is unsymmet-
rical and there are two ways to obtain such C,C¢-disubsti-
tuted carboranes: either by desymmetrisation of ortho-
carborane6 or by cycloaddition of decaborane to an un-
Abstract: The preparation of an ortho-carborane derivative bearing
both carbohydrate and amino acid substituents is presented; open-
ing of a glucofuranuro-g-lactone derivative with propargylamines,
cycloaddition of decaborane to an acetylenic bond and amidation
with a N-Fmoc-glutamate derivative are the key-steps in this syn- symmetrically substituted triple bond.7 This latter ap-
thesis.
proach was favoured because it avoids the use of the
expensive ortho-carborane as the starting material but
also because formation of the boron cage can be planned
at a late stage of the synthesis, thus bringing flexibility.
Key words: amino acids, boron, carbohydrates, carboranes, cyclo-
additions
ortho-Carboranes are boron-rich clusters,1 which are of
current interest for applications in medicinal chemistry.2
Conjugation of carboranes to carbohydrates endows these
(otherwise very) lipophilic boron cages with aqueous sol-
ubility; on the other hand, amino acid units can be grafted
to allow carboranes incorporation into peptides.2 To
confer these two properties to a carborane core 3 we have
prepared a glycosylated carboranyl amino acid, thus en-
compassing both carbohydrate and amino acid units,
which has been designed (Figure 1) as follows.
R'
R''
O
N
O
R''HN
RO
RO
O
O
R'
O
OH
O
O
O
O
2 : R = H
3 : R = TBDMS
4 : R = R' = R'' = H (100%)
5 : R = TBDMS ; R' = R'' =H (62 %)
6 : R = R' = H ; R'' = CH3 (87%)
7 : R = R'' = H ; R' = CH2OH (98%)
affinity for
GLUT
for conjugation
to peptide
boron-rich
moiety
Scheme 1
To introduce a glucose unit, advantage was taken of the
peculiar reactivity at C-6 of the (readily available) gluco-
furanurono-g-lactone acetals 28 or 39 as ring opening by
amines is known to occur under particularly mild condi-
tions.10,11 For this work (Scheme 1) amidation with prop-
argylamine occurred smoothly, which gave 4 and 5,
respectively. Efficient results were also achieved when 2
was treated with N-methyl-propargylamine (to give 6) or
4-hydroxy-but-2-ynamine12 (to give 7); interestingly,
when treated with 1,4-diamino-but-2-yne,12 which was
followed by acetal formation, 2 gave 8 (Figure 2), which
therefore arose from a double condensation.13
CO2H
O
carbohydrate
(brings hydrophilicity)
NHFmoc
amino acid
ortho-carborane
= C
= BH
Figure 1
Solid phase peptide assembly of N-Fmoc-protected
carboranyl amino acids has been shown to proceed effi-
ciently,4 which led to our choice of a N-a-Fmoc amino
acid pendant side chain to enable subsequent conjugation.
With regard to the carbohydrate unit, D-glucose was se-
lected as it could allow recognition by the glucose trans-
port proteins (GLUTs), provided linkage by a non-binding
region (such as the non-reducing end of glucose).5
Protection of the free hydroxyl groups of 4 and 5 needed
to be performed as exchangeable protons are know to
have adverse effects against the cycloaddition of decabor-
ane to acetylenic bonds.14 When masked as acetates (from
compound 4) or as silyl ethers (from compound 5) com-
plex mixtures were observed after reaction with decabor-
ane but when protected together as a benzylidene acetal,15
carborane formation was effective. However, to avoid
introduction of a new stereocenter, an isopropylidene
Synlett 2003, No. 10, Print: 05 08 2003.
Art Id.1437-2096,E;2003,0,10,1399,1402,ftx,en;G08103ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1400
C. Thimon et al.
LETTER
Thus, a glucosyl-carborane bearing a pendant N-Fmoc
amino-acid side-chain, 17, was obtained in 7 steps (31%
overall yield from 2). This boron cluster is of interest not
only because its preparation provides a methodology for
assembling carbohydrates and amino acids to a carborane
core, but also because solid phase peptide assembly could
enable its auto assembly towards the preparation of hydro-
philic polycarboranes oligomers. This could be of interest
for conveying large quantities of boron-1025 to targets be-
fore Boron Neutron Capture Therapy (BNCT) treat-
ments.26
Figure 2
acetal seemed preferable. Using 2,2-dimethoxypropane/
acetone under acidic catalysis, an acetalation procedure,16
which consistently gave good results in this work, com-
pounds 9 and 10 were obtained from 4 and 6,
respectively(Figure 3). Remarkably, when reacting 7 un-
der those conditions, the mixed acetal 11 arising from a
reaction of the primary hydroxyl group,17 was formed.
Compound 11 was selectively deprotected (without isola-
tion) to give the desired alcohol 1218 that was subsequent-
ly converted to mesylate 13.19 Thus, 13 was obtained in 4
steps (86% overall yield) from 2 (Figure 3).
Acknowledgement
CT is grateful to the Région Rhone-Alpes for a 6-months EURO-
DOC fellowship and LP is grateful to MIUR (COFIN 2001) and
Università del Piemonte Orientale (ex 60%) for financial support.
References
(1) Bregadze, V. I. Chem. Rev. 1992, 92, 209.
(2) Valliant, J. F.; Guenther, K. J.; King, A. S.; Morel, P.;
Schaffer, P.; Sogbein, O. O.; Stephenson, K. A. Coord.
Chem. Rev. 2002, 232, 173.
(3) For examples in the meta-carborane series, see: (a) Das, B.
C.; Kabalka, G. W.; Srivastava, R. R.; Bao, W.; Das, S.; Li,
G. J. Orgmet. Chem. 2000, 614-615, 255. (b) Das, B. C.;
Das, S.; Li, G.; Bao, W.; Kabalka, G. H. Synlett 2001, 1417.
(c) Kabalka, G. W.; Das, B. C.; Das, S.; Li, G.; Srivastava,
R. R.; Natarajan, N.; Khan, M. K. Coll. Czech. Chem.
Commun. 2002, 67, 836.
R'
R''
N
O
O
O
O
O
(4) Kane, R. R.; Pak, R. H.; Hawthorne, F. W. J. Org. Chem.
1993, 58, 991.
O
(5) (a) Holman, G. D.; Rees, W. D. Biochim. Biophys. Acta
1982, 685, 78. (b) Joost, H.-G.; Thorens, B. Mol. Membr.
Biol. 2001, 18, 247. (c) Dwyer, D. S.; Vannucci, S. J.;
Simpson, I. A. Int. Rev. Neurobiol. 2002, 51, 159.
(d) Medina, R. A.; Owen, G. I. Biol. Res. 2002, 35, 9.
(6) (a) Gomez, F. A.; Hawthorne, M. F. J. Org. Chem. 1992, 57,
991. (b) Vinas, C.; Benakki, R.; Texidor, F.; Casabo, J.
Inorg. Chem. 1995, 34, 991.
9 : R' = R'' = H (81%)
10 : R' = H ; R'' = CH3 (87%)
11 : R' = CH2O-CH(OCH3)CH3 ; R'' =H
12: R' = CH2OH ; R'' = H (90%, 2 steps)
13: R' = CH2OSO2CH3 ; R'' = H (98%)
Figure 3
(7) Heying, T. L.; Ager, J. W. Jr.; Clark, S. L.; Mangold, D. J.;
Goldstein, H. J.; Hillman, M.; Polak, R. J.; Szymanski, J. W.
Inorg. Chem. 1963, 2, 1089.
(8) Kitahara, T.; Ogawa, T.; Naganuma, T.; Masui, M. Agric.
Biol. Chem. 1974, 38, 2189.
(9) Bleriot, Y.; Veighey, C. R.; Smelt, K. H.; Cadefeau, J.;
Stalmans, W.; Biggadike, K.; Lane, A. L.; Muller, M.;
Watkin, D. J.; Fleet, G. W. J. Tetrahedron: Asymmetry 1996,
7, 2761.
(10) (a) Owen, L. N.; Peat, S.; Jones, W. G. J. J. Chem. Soc. 1941,
339. (b) Abbadi, M.; Holman, G. D.; Morin, C.; Rees, W. D.;
Yang, J. Tetrahedron Lett. 1999, 40, 5861.
Substitution of 13 with cysteine was next attempted so as
to link an amino acid moiety in a straightforward manner
(Scheme 2). Deprotonation of the thiol group of cysteine
with sodium ethoxide has been shown to occur without ra-
cemisation,20 which allowed ligation of cysteine to mesy-
late 13 to afford 14. Subsequent orthogonal protections of
the amine and of the carboxylic groups (see Scheme 2)
were performed as, here again, these functional groups
needed to be protected before reaction with decaborane.
However, despite such masking of exchangeable protons,
no formation of carborane could be observed. This result
was unexpected as thiopropargylic derivatives are known
to react with decaborane uneventfully.21 In case that the
sulfur atom of 14 acted itself as a ligand of decaborane,
thus inhibiting the process, the reaction was next attempt-
ed in the presence of an excess of diethyl sulfide but with-
out success. Therefore, 13 was next converted to 1522 and
condensed with FmocGlu(OH)OBn, which yielded 16.23
Reaction of 16 with decaborane proceeded then satisfac-
torily to give 17.24
(11) General procedure for opening of lactone 2 with amines (5–
15 mmole scale): To a solution of lactone in acetonitrile (10
mL/mmole) was added an excess of amine (2–4 equiv) and
the mixture was stirred overnight after which time volatiles
were removed. Compound 4 was obtained quantitatively
without purification while isolation of pure 6 (87%) and 7
(98%) was performed by flash chromatography on silica gel
(eluent:CH2Cl2/CH3OH, 95:5).
4: 1H NMR (300 MHz,, CDCl3): 7.38 (t, J = 5.4 Hz, 1 H,
NH); 5.97 (d, J1,2 = 3.6 Hz, 1 H, H-1); 4.84–4.07 (m, 8 H);
2.32 (t, J1¢,3¢ = 2.5 Hz, 1 H, H-3¢); 1.48 (s, 3 H, CH3); 1.31 (s,
3 H, CH3). 13C NMR (75 MHz, CDCl3): 172.3 (C-6); 112.2
(C-1); 105.2 [C(CH3)2]; 85.1; 80.8; 79.1 (C-3¢); 75.2; 72.0
Synlett 2003, No. 10, 1399–1402 © Thieme Stuttgart · New York

LETTER
Synthesis of a Glycosylated ortho-Carboranyl Amino Acid
1401
H
N
NH2
H
N
OMs
O
O
O
O
O
O
O
O
NH4OH
O
O
O
O
15
13
1) cysteine, EtONa
2) Fmoc - succinimide
3) BnOH, DCC
52% overall
FmocGlu(OH)OBn, DCC, CH2Cl2
82%
H
N
S
H
N
NH
O
O
CO2Bn
CO2Bn
O
O
O
O
O
O
O
NHFmoc
NHFmoc
O
O
O
O
16
14
B10H10, CH3CN 46%
H
N
O
O
O
O
CO2Bn
NHFmoc
O
N
H
O
O
17
Scheme 2
(C-2¢); 69.7; 29.2 (C-1¢); 26.8 (CH3); 26.2 (CH3). 6: 1H NMR
(300 MHz,, CDCl3): 5.96 (d, J1,2 = 3.5 Hz, 1 H, H-1); 4.76–
4.43 (m, 4 H); 4.10–3.82 (m, 3 H); 3.40–3.10 (m); 3.16 (s,
H-1¢¢); 3.09 (s, H-1); 2.32 (t, J1¢-3¢ = 2.4 Hz, H-3¢); 2.26 (t,
treatment of the crude solid with Dowex 1X8 R3N+Cl– pre-
washed with 4% NaOH aq solution. The brown oil thus
obtained should be used without delay. (b) For more
information on 4-hydroxy-but-2-ynamine, see: Marszak-
Fleury, A.; Laroche, J. Bull. Soc. Chim. Fr. 1963, 1270. (c)
For more information on synthetic procedure, see:Dumez,
E.; Faure, R.; Dulcere, J.-P. Eur. J. Org. Chem. 2001, 2577.
(d) Analytical data for the tosylate salt: mp 94–96 °C. 1H
NMR (300 MHz, D2O) 7.60 (d, 2 H, J = 7.1 Hz, ArH), 7.27
(d, 2 H, J = 7.1 Hz, ArH), 4.18 (s, 2 H, H-4), 3.77 (s, 2 H, H-
1), 2.30 (s, 3 H, CH3). 13C NMR 140.0 (Cquat Ar), 137.9
(Cquat Ar); 127.2 (CH Ar), 123.1 (CH Ar), 82.5 and 73.8 (C-
2, C-3), 47.1 and 27.0 (C-1, C-4), 18.3 (CH3). (e)
Similarly, but-2-yn-1,4-diamine was prepared from 1,4-bis-
mesyloxy-but-2-yne, see: Haslinger, H.; Soloway, A. H. J.
Med. Chem. 1966, 9, 792. (f) Analytical data for its bis
mesylate salt: mp 160 (dec.) 1H NMR (300 MHz, D2O) 3.77
(s, 4 H, H-1/H-4), 2.58 (s, 6 H, CH3). 13C NMR 79.1 (C-2/
C-3), 39.2 (CH3), 29.8 (C-1/C-4).
J
1¢-3¢ = 2.4 Hz, H-3¢); 1.46 (s, 3 H, CH3); 1.31 (s, 3 H, CH3).
13C NMR (75 MHz, CDCl3): 172.9 and 172.8 (C-6); 112.1
[C(CH3)2]; 112.0 [C(CH3)2]; 105.6 (C-1); 84.5; 82.7*; 77.9;
75.7; 75.6; 73,3; 72.7; 65.9; 39.0 (C-1¢); 37.6 (C-1¢); 34.6 (C-
1¢¢); 34.1 (C-1¢); 26.9 (CH3); 26.3 (CH3). 7 1H NMR (300
MHz, CD3OD): 5.90 (d, J1,2 = 3.6 Hz, 1 H, H-1); 4.47 (d,
J1,2 = 3.6 Hz, 1 H, H-2); 4.34–4.37 (dapp, Japp = 6.0 Hz, 1 H,);
4.26–4.16 (m, 4 H); 4.08–4.05 (tapp, Japp = 1.9 Hz, 2 H,); 1.44
(s, 3 H, CH3); 1.29 (s, 3 H,CH3). 13C NMR (75 MHz,
CD3OD): 174.3 (C-6); 112.9 [C(CH3)2]; 106.4 (C-1); 86.4;
82.3; 81.9; 81.3; 75.9; 71.0; 50.7 (C-4¢); 29.6 (C-1¢); 271
(CH3); 264 (CH3). [a]20D –13 (c 6; MeOH).
(12) (a) 4-Hydroxy-but-2-ynamine was prepared by overnight
stirring of a solution of 4-tosyloxybut-2-yn-1-ol in
ammonium hydroxide, followed by evaporation and
Synlett 2003, No. 10, 1399–1402 © Thieme Stuttgart · New York

1402
C. Thimon et al.
LETTER
(13) Such a derivative could be useful in the preparation of bis-
glycosyl-carboranes (Panza, L. et al., manuscript in
preparation), see: Giovenzana, G. B.; Lay, L.; Monti, D.;
Palmisano, G.; Panza, L. Tetrahedron 1999, 55, 14123.
(14) Fein, M.; Grafstein, D.; Paustian, J. E.; Bobinski, J.;
Lichstein, B. M.; Myes, N.; Schwartz, N. S.; Cohen, M. S.
Inorg. Chem. 1963, 2, 1115.
(15) Bagget, N.; Smithson, A. Carbohydr. Res. 1982, 108, 59.
(16) Blériot, Y.; Masaguet, C. F.; Charlwood, J.; Winchester, B.
G.; Lane, A. L.; Crook, S.; Watkin, D. J.; Fleet, G. W. J.
Tetrahedron 1997, 53, 15135.
H, CH3). 13C NMR (75 MHz, CDCl3): 169.5 (C-6); 112.3
[C(CH3)2]; 106.4 (C-1); 101.1 [C(CH3)2]; 84.3; 83.6; 79.1;
74.8; 71.8 (C-2, C-3, C-4, C-5); 67,1; 31.6 (C-4¢); 29.1 (C-
1¢); 27.1 (CH3); 26.6 (CH3); 24.6 (CH3); 23.8 (CH3).
(23) N-Fmoc amino acid 16: Condensation of amine 15 in CH2Cl2
with commercially available benzyl ester of N-Fmoc
glutamic acid in the presence of 1 equiv of DCC: 82%. 1H
NMR (300 MHz, CDCl3): 7.75–7.26 (m, 13 H, H ar); 6.71 (s
l, 1 H, NH); 6.59 (s l, 1 H, NH); 6.04 (dapp, Japp = 7.95 Hz,
NH); 6.00 (dapp, Japp = 3.7 Hz, 1 H, H-1); 5.15 [s, 2 H, CH2
(Bn)];.4.58–3.98 (m, 12 H); 2.50–1.50 (m l, 4 H); 1.44 (s,
CH3); 1.38 (s, CH3); 1.34 (s, CH3); 1.29 (s, CH3). 13C NMR
(75 MHz, CDCl3): 171.9 (C-5¢¢); 169.7 (C-6); 156.3
(17) Barili, P. L.; Berti, G.; Catelani, G.; Colonna, F.; Marra, A.
Tetrahedron Lett. 1986, 27, 2307.
(18) To a solution of 7 (1g; 3.3 mmol) in acetone (30 mL) were
added under stirring 2,2- dimethoxypropane (20 mL, 164
mmol; 50 equiv) and camphorsulfonic acid (77 mg, 0.33
mmol; 0.1 equiv). After 24 h stirring, NaHCO3 (2 g) was
added and after further 15 min stirring the mixture was
filtered on celite. The oil (crude 11) obtained after
evaporation of the volatiles was dissolved in methanol (50
mL) containing AcOH (170 mL of 60% aqueous solution)
and stirred at 50 °C for 80 min then cooled rapidly to r.t.
Sodium hydrogen carbonate (2 g) was added and the solution
was stirred for 15 min before filtration. Compound 12 (1.010
g, 3 mmol 90%) was obtained pure after column
[OC(O)NH]; 143.9, 143.7, 141.3 (Cquat Fmoc); 135.2
(OCH2C); 128.6; 128.5; 128.3; 127.7; 127.1; 125.1; 120.0;
112.3 [C(CH3)2]; 106.3 (C-1); 101.2 [C(CH3)2]; 83.5; 79.4;
79.3; 78.2; 77.6; 74.8; 71.8; 67,.2 (OCH2CH); 67.0
(OCH2CH); 53.7 (C-2¢¢); 47.1 (OCH2CH); 32.0; 29.2; 28.9;
27.9; 27.0 (CH3); 26.5 (CH3); 24.4 (CH3); 23.7 (CH3).
(24) Carborane 17: Under argon, a solution of decaborane (20
mg; 0.17 mmol, 1.3 equiv) in toluene (2 mL) and acetonitrile
(68 mL; 1.3 mmol, 10 equiv) was heated at 110 °C for 1 h
then cooled to r.t. before the addition of 16 (100 mg; 0.13
mmol). The mixture was stirred at reflux for 5 h and
methanol (0.5 mL) was added to destroy the excess of
decaborane. After evaporation of the volatiles, column
chromatography on silica gel (CH2Cl2/EtOAc: 8.5/1.5) gave
carborane 17 (50 mg, 46%) as a white powder. 1H NMR (300
chromatography (silica gel, CH2Cl2/CH3OH: 95/5) as a
white foam 1H NMR (300 MHz, CDCl3): 6.57 (l s, 1 H, NH);
6.04 (d, J1,2 = 3.7 Hz, 1 H, H-1); 4.60-4.50 (m, 2 H); 4.30–
4.11 (m, 6 H); 1.49 (s, 3 H, CH3); 1.42 (s, 3 H, CH3); 1.39 (s,
3 H, CH3); 1.32 (s, 3 H, CH3). 13C NMR (75 MHz, CDCl3):
169.3 (C-6); 112.1 [C(CH3)2)]; 107.8 (C-1); 101.0
[C(CH3)2]; 83.0; 82.2; 80.3 (C-2¢, C-3¢); 78.6; 74.2; 71.2;
50.3 (C-4¢); 28.8 (C-1¢); 26.5 (CH3); 26.0 (CH3); 23.9 (CH3);
23.2 (CH3).
MHz, CDCl3): 7.74 (dapp, Japp = 7.5 Hz, 2 H); 7.58 (dapp
,
Japp = 7.2 Hz, 2 H); 7.5–7.2 (m, 11 H); 6.00 (d, J = 3.6 Hz, 1
H, H-1); 5.87 (d, J = 7.9 Hz, 1 H, NH); 5.17 (s l, 2 H,
CCH2O); 4.55–4.08 (m, 12 H); 2.28–2.02 (m); 1.44 (s, CH3);
1.39 (s, CH3); 1.36 (s, CH3); 1.28 (s, CH3). 13C NMR
(75 MHz, CDCl3): 172.4 (C-1¢¢); 171.7 (NHCO); 170;6
(NHCO); 156.6 [OC(O)NH]; 143.9; 143.7; 141.4 (Cquat
Fmoc); 135.2 (OCH2C); 128.7; 128.6; 128.4; 127.8; 127.2;
125.2; 120.1; 112.6 [C(CH3)2]; 106.5 (C-1); 101.6
[C(CH3)2]; 83.5; 81.0 (CB); 79.7; 78.2; 75.1; 71.8; 67.5
(OCH2CH); 67.2 (OCH2CH); 53.6 (C-2¢¢); 47.2 (OCH2CH);
42.0 (CH2N); 41.1 (CH2N); 32.0; 28.4; 27.1 (CH3); 26.6
(CH3); 24.2 (CH3); 23.7 (CH3). Anal. C43H57B10N3O11–0.25
CH2Cl2. Calcd.: C 56.39, H 6.29, B 11.73, N 4.56; found C
56.48, H 6.35, B 11.75, N 4.55. MS (electrospray):
(M + Na)+ centered at m/z = 923.5 (cluster from m/z = 919.5
to 926.5 with relative intensities matching the calculated
spectrum for C43H57B10N3O11).
(19) Mesylate 13 was obtained conventionally (triethylamine,
mesyl chloride, 2.2 equiv each, in CH2Cl2, 2 h, 98%). 1H
NMR (300 MHz, CDCl3): 6.53 (s l, 1 H, NH); 6.04 (d, J1,2
=
3.7 Hz, 1 H, H-1); 4.90–4.85 (m, 2 H, W1/2 = 33 Hz); 4.60–
4.50 (m, 2 H); 4.10–4.25 (m, 4 H); 3.12 (s, 3 H, H-1¢¢); 1.49
(s, 3 H, CH3); 1.43 (s, 3 H, CH3); 1.40 (s, 3 H, CH3); 1.32 (s,
3 H, CH3). 13C NMR (75 MHz, CDCl3): 169.8 (C-6); 112.4
[C(CH3)2]; 106.5 (C-1); 101.3 [C(CH3)2]; 85.6 (CCH2);
83.6; 79.3; 75.6 (CCH2); 74.9; 71.9; 57.6 (C-4¢); 39.1 (C-
1¢¢); 28.9 (C-1¢); 27.2 (CH3); 26.6 (CH3); 24.6 (CH3); 23.9
(CH3).
(20) Cundari, S.; Dalpozzo, R.; De Nino, A.; Procopio, A.;
Sindona, G.; Athanassopulos, K. Tetrahedron 1999, 55,
10155.
(21) Nabakka, J. M.; Harwell, D. E.; Knobler, C. B.; Hawthorne,
M. F. J. Organomet. Chem. 1998, 550, 423.
(25) For a synthesis of 10B enriched decaborane, see: Adams, L.;
Tomlison, S.; Wang, J.; Hosmane, S. N.; Maguire, J. A.;
Hosmane, N. S. Inorg. Chem. Commun. 2002, 5, 765.
(26) For some reviews about ‘chemistry and BNCT’, see:
(a) Hawthorne, M. F. Angew. Chem., Int. Ed. Engl. 1993, 32,
950. (b) Morin, C. Tetrahedron 1994, 50, 12521.
(22) Amine 15 was obtained by reaction of mesylate 13 with 25%
aq. ammonia/dioxane (5/1) 35 °C, 80 min Yield: 95%. 1H
NMR (300 MHz, CDCl3): 6.56 (s l, 1 H, NH); 6.04 (d, J1-2
=
(c) Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong, F.-G.;
Barth, R. F.; Codogni, I. W.; Wilson, J. G. Chem. Rev. 1998,
98, 1515.
3.7 Hz, 1 H, H-1); 4.59–4.55 (m, 2 H); 4.24–4.08 (m, 4 H);
3.46–3.44 (m, 2 H, Japp = 2 Hz); 1.70 (s l, 2 H, NH2); 1.48 (s,
3 H, CH3); 1.43 (s, 3 H, CH3); 1.39 (s, 3 H, CH3); 1.32 (s, 3
Synlett 2003, No. 10, 1399–1402 © Thieme Stuttgart · New York