Mendeleev Commun., 2014, 24, 245–246
0.4
0.3
0.2
0.1
0.0
0.4
0.3
0.2
0.1
0.0
1
2
2
3
4
3
2
250 300 350 400 450 500 550 600 650 700
4
1
l/nm
250 300 350 400 450 500 550 600 650 700
Figure 3 Absorption spectra of compound 4 in DMSO, 25°C: (1) original
solution, (2) after UV illumination at 365 nm (3) after subsequent storage in
the dark for 1 min and (4) after subsequent storage in the dark for 5 min.
l/nm
Figure 2 Absorption spectra of compound 2 in DMSO, 25°C: (1) original
solution, (2) after UV illumination at 365 nm, (3) after subsequent storage
in the dark for 3 min and (4) after subsequent storage in the dark for 10 min.
spiropyran moieties are separated by spacers that are stable under
physiological conditions.
analogue 4 was obtained by the reaction of HBTU-activated
starting compound 3 with commercially available N-(2-amino-
ethyl)maleimide.‡ The low yield of the product (9%) may be
explained by non-optimum conditions of product isolation.
Preliminary study of the photochromic properties of labels 2
and 4 showed that the principal behaviour of these compounds
nearly did not differ from that of other 6'-nitro-substituted spiro-
benzopyrans.8 UV irradiation (365 nm) of maleimides 2 and 4 in
DMSO solutions resulted in colouring (a growth in the absorption
mono band of the spiropyran merocyanine form at 560–570 nm).
Upon storage of the resulting samples in the dark, the absorption
curves slowly returned to the original positions (Figures 2 and 3).
As a result, hitherto unknown maleimide spirobenzopyrans
2 and 4 have been obtained as potential photochromic markers
for macromolecules with sulfhydryl groups. The maleimide and
This study was supported by the Grant of the Russian Federa-
tion President for young scientists (MK-6877.2012.4) and the
Russian Foundation for Basic Research (grant no. 12-04-31190).
References
1 (a) J. D. Gregory, J. Am. Chem. Soc., 1955, 77, 3922; (b) D. G. Smyth,
O. O. Blumenfeld and W. Konigsberg, Biochem. J., 1964, 91, 589.
2 (a) N. Fujii, M. Kaneda, R. Misu, T. Noguchi, H. Ohno, S. Oishi, S. Setsuda,
B. Evans, J.-M. Navenot and S. C. Peiper, Bioorg. Med. Chem. Lett., 2013,
23, 2628; (b) T. Ito, M. Inoue, K. Akamatsu, E. Kusaka, K. Tanabe and
S.-I. Nishimoto, Bioorg. Med. Chem. Lett., 2011, 21, 3515; (c) C. Waengler,
P. Bartenstein, B. Waengler, M. Schaefer and R. Schirrmacher, Bioorg.
Med. Chem., 2011, 19, 3864; (d) P. D. Garimella,A. Datta, D. W. Romanini,
K. N. Raymond and M. B. Francis, J. Am. Chem. Soc., 2011, 133, 14704;
(e) F. Liu,A.-S.-Y. Ni,Y. Lim, B. Xing, H. Mohanram and S. Bhattacharjya,
Bioconjugate Chem., 2012, 23, 1639; (f)V. Tolmachev, M. Altai, A. Orlova,
M. Sandstroem,A. Perols,A.-E. Karlstroem and F. Boschetti, Bioconjugate
Chem., 2011, 22, 894.
‡
5'-[N-(2-Maleimidoethyl)carbamoyl]-1',3',3'-trimethyl-6-nitro-1',3'-di-
3 (a) W. W. Cleland, Biochemistry, 1964, 3, 480; (b) S. Klueter, C. Gruetter,
M. Rabiller, J. R. Simard, V. Pawar, M. Getlik, D. Rauh and T. Naqvi,
J. Med. Chem., 2010, 53, 357.
4 M. Harada, M. Sisido, J. Hirose and M. Nakanishi, Bull. Chem. Soc. Jpn.,
1994, 67, 1380.
5 (a) T. Sakata, Y. Yan and G. Marriott, J. Org. Chem., 2005, 70, 2009;
(b) G. Marriott, T. Sakata and Y. Yan, US Patent 0195309(A1), 2007.
6 A. V. Laptev,A.Yu. Lukin, N. E. Belikov,V.A. Barachevskii, O.V. Demina,
A. A. Khodonov, S. D. Varfolomeev and V. I. Shvets, Mendeleev Commun.,
2013, 23, 145.
hydrospiro[chromene-2,2'-indole] 4. O-(Benzotriazol-1-yl)-N,N,N',N'-
tetramethyluronium hexafluorophosphate (coupling reagent for peptide,
HBTU) (200 mg, 0.85 mmol) was added to a solution of 1',3',3'-trimethyl-
6-nitro-1',3'-dihydrospiro[chromene-2,2'-indole]-5'-carboxylic acid 3
(400 mg, 1.09 mmol) in 20 ml of DMF cooled to 0°C. The mixture was
agitated for 10 min with a magnetic stirrer, then a solution of N-(2-amino-
ethyl)maleimide [freshly prepared from the corresponding hydrotrifluoro-
acetate salt (140 mg, 0.55 mmol) neutralized with N-methylmorpholine
(200 ml, 2.83 mmol)] in 2 ml of dry DMF was added. The mixture was
agitated overnight, then the solvent was removed in vacuo. The target
spiropyran 4 was isolated using column chromatography on alumina in a
hexane–ethyl acetate system.Yield 50 mg (9%). Rf 0.4. UV-VIS [DMSO,
7 M. A. Walker, J. Org. Chem., 1995, 60, 5352.
8 (a) Photochromism: Molecules and Systems, eds. H. Durr and H. Bouas-
Laurent, Elsevier, Amsterdam, 2003; (b) E. R. Zakhs, V. M. Martynova and
L. S. Efros, Chem. Heterocycl. Compd., 1979, 15, 351 (Khim. Geterotsikl.
Soedin., 1979, 435); (c) O. V. Demina, P. P. Levin, N. E. Belikov, A. V.
Laptev, A. Yu. Lukin, V. A. Barachevsky, V. I. Shvets, S. D. Varfolomeev
and A. A. Khodonov, J. Photochem. Photobiol. A: Chem., 2013, 270, 60;
(d)A. V. Laptev, A.Yu. Lukin, N. E. Belikov, R. V. Zemtsov, V. I. Shvets,
O. V. Demina, S. D. Varfolomeev, V. A. Barachevskii andA.A. Khodonov,
High Energy Chem., 2010, 44, 211 (Khim. Vys. Energ., 2010, 44, 239).
l
max/nm (lg e)]: 277 (4.85), 342 (4.42); lMmaCx = 569 nm. 1H NMR (CDCl3)
d: 1.17 (s, 3H, C3'aH3), 1.30 (s, 3H, C3'bH3), 2.77 (s, 3H, C1'H3), 3.65 (m,
2H, C1''H2), 3.82 (m, 2H, C2''H2), 5.83 (d, 1H, H3, J 10.4 Hz), 6.53 (d,
1H, H7', J 8.1 Hz), 6.57 (t, 1H, NH, J 4.0 Hz), 6.73 (s, 2H, Hmaleimide), 6.76
(d, 1H, H8, J 9.0 Hz), 6.92 (d, 1H, H4, J 10.4 Hz), 7.56 (d, 1H, H4', J 1.6 Hz),
7.59 (dd, 1H, H6', J 8.1 and 1.8 Hz), 8.0 (s, 1H, H5), 8.02 (d, 1H, H7, J 9.0
and 2.7 Hz). 13C NMR (CDCl3) d: 19.88 (Me), 25.87 (Me), 28.90 (NMe),
38.39 (NHCH2), 40.90 (C3'), 41.55 (NCH2), 106.80 (Cspiro), 114.21 (C7'H),
118.62 (C8H), 121.43 (C4H), 122.44 (C5H), 123.67 (C6'H), 125.88
(C3H), 127.72 (C7H), 127.90 (C4'H), 128.75 (C10H), 134.02 (C9'H), 134.93
(2CHmaleimide), 135.95 (C5'H), 140.92 (C6H), 148.51 (C8'H), 159.73 (C9H),
163.69 (C=O), 168.24 (2C=Omaleimide). LC-MS (UV254), m/z:489.5 [M+1]+.
Found (%): C, 63.55; H, 5.30; N, 11.26. Calc. for C26H24N4O6 (%): C, 63.93;
H, 4.95; N, 11.47.
Received: 28th October 2013; Com. 13/4235
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