1702, 1656, 1509, 1231. lmax/nm (MeOH) (e): 206 (26500), 226 (16000),
254 (18 600), 274 (11100). dH (360 MHz, CDCl3) 1.96 (3 H, s, T-Me) 3.78
(3 H, s, OMe), 4.24 (1 H, dd, 10.3 and 4.1 Hz, H-4a), 4.30 (1 H, dd, 10.3 and
5.6 Hz, H- 4b), 5.42 (1 H, m, H-3), 5.47 (1 H, dd app. d, 17.4 Hz, H-1a), 5.52
(1 H, dd app. d, 10.8 Hz, H-1b), 6.07 (1 H, ddd, 17.3, 10.7 and 5.7 Hz, H-2),
6.85 (4 H, s, Ar), 7.35 (1 H, s, T-6), 7.47 (2 H, t, 7.8 Hz, Bz), 7.64 (1 H, t,
7.4 Hz, Bz), 7.90 (2 H, dd app. d, 7.8 Hz, Bz). dC (360 MHz, CDCl3): 12.46
(T-Me), 55.62 (OMe), 55.83 (C-3), 68.48 (C-4), 110.34 (T-5), 114.74 (Ar-
o), 115.70 (Ar-m), 120.89 (C-1), 128.98 (Bz-m), 130.31 (Bz-o), 131.56
(C-2), 131.63 (Bz-i), 134.78 (Bz-p), 138.19 (T-6), 149.96, 152.00 (Ar-i and
usually encountered in thymine derivatives is prevented by
carrying out the reaction in dilute medium and also by the
efficiency of the intramolecular photocycloaddition.
Interestingly, independent irradiation of N3-benzoylthymine
and 4-phenoxy-3-(N3-benzoylthymin-1-yl)but-1-ene 3, under
the same conditions as described, resulted in complete substrate
consumption yielding mainly polar constituents, in which loss
of the benzoyl group was evident from the NMR data.
Analogous thymine-unprotected compounds, such as
.
-p), 154.51 (T-2), 162.60 (T-4), 168.80 (Bz-CO). MS: 407 (M+ + H+; 10),
4-(4-methoxyphenoxy)-3-(thymin-1-yl)but-1-ene
4 and 4-
105 (100). For 2: mp 173.7 °C. Rf (pentane–ethyl acetate, 6:4): 0.53. n
(KBr)/cm21 1743, 1700, 1673, 1437, 1232, 897, 796, 730. lmax/nm
(MeOH) (e): 206 (21500), 250 (16800), 284 (3900). dH (Gemini 200 MHz,
CDCl3) 1.39 (3 H, s, Me12), 3.53 (1 H, dd, 212.3 and 9.4 Hz, H-4a), 3.60
(3 H, s, OMe), 3.65 (1 H, d, 1.2 Hz, H-13), 4.01 (1 H, br d, J 6.9 Hz, H-11),
4.03 (1 H, dd, 212.2 and 8.0 Hz, H-4b), 4.58 (1 H, br d, 6.8 Hz, H-10), 5.03
[1 H, qt, 8 Hz (3 3), H-3], 5.32 (1 H, dt, 10.3 and 21.3 Hz, H-1a), 5.34 (1
H, dt, 17.3 and 21.3 Hz, H-1b), 5.75 (1 H, ddd, 17.3, 10.3 and 5.6 Hz, H-2),
6.07 (1 H, dt, 10.3 and 1.3 Hz, H-7); 6.15 (1 H, dd, 10.1 and 1.9 Hz, H-8),
7.50 (2 H, tm, 7.4 Hz, Bz-o), 7.64 (1 H, tt, 7.3 and 1.4 Hz, Bz-p), 7.94 (2 H,
dm, 7.1 Hz, Bz-m). dC (Gemini 200 MHz, CDCl3) 16.84 (Me12), 40.24
(C-12), 47.72 (C-11), 51.58 (C-3), 54.84 (OMe), 56.56 (C-13), 62.41 (C-4),
70.00 (C-6), 87.81 (C-10), 118.71 (C-1), 124.90 (C-7), 129.04 (Bz-m),
129.35 (C-8), 130.12 (Bz-o), 131.64 (C-2), 132.59 (Bz-i), 134.62 (Bz-p),
phenoxy-3-(thymin-1-yl)but-1-ene 5, proved to be light-stable,
even after prolonged irradiation (24 h). It is, therefore, deduced
that the presence of both the para-methoxy and the N3-benzoyl
groups is required in order to direct the intramolecular arene–
alkene photocycloaddition thereby showing the sensitivity of
this reaction to subtle and unexpected substituent effects. The
para-methoxy group apparently creates suitable electronic
conditions for ortho addition, while it remains to be clarified
whether the benzoyl group activates or the secondary amide
inhibits photocycloaddition.
In most instances, the ortho adducts, resulting from intra-
molecular arene–alkene photocycloaddition, suffer from further
reactions depending on the varying stabilities of the particular
compounds formed in the cascade. The bicyclo[4.2.0]octa-
2,4-diene unit, present in such ortho photoadducts, normally
rearranges on heating into a cyclooctatriene, which subse-
quently gives a mixture of [2 + 2] photocycloadducts. Only
occasionally have primary ortho photoadducts been isolated as
stable compounds, as was found on irradiation of penta-
fluorophenylprop-2-enyl ether,9 2-methyl-6-(4-fluorophenyl)-
.
150.51 (C-15), 155.48 (C-9), 169.38 (C-17), 170.57 (Bz-CO). MS: 407 (M+
+ H+; 5); 105 (100).
§ Cleavage of epoxides usually requires attack by reactive nucleophiles as
described by Posner and Rogers (J. Am. Chem. Soc., 1977, 99, 8208). We
were able to effect the reaction using 4-methoxyphenolate in Me2SO (57%).
In the absence of the activating para-methoxy group the yield is
significantly decreased (20%).
hex-2-ene10
and
1-(2-methoxybenzyloxy)-3-methylbut-
References
2-ene.11 In the present case, after heating 2 in refluxing THF for
several hours we were not able to detect cyclooctatriene-like
structures, nor was there any evidence for a Diels–Alder-type
reaction between the alkene and the cyclohexa-1,3-diene units
present in 2.
1 J. Cornelisse, Chem. Rev., 1993, 93, 615.
2 D. De Keukeleire, S.-L. He, D. Blakemore and A. Gilbert, J. Photo-
chem. Photobiol. A: Chem., 1994, 80, 233.
3 D. De Keukeleire, S.-L. He and C.-Y. Wang, University of Gent,
Faculty of Pharmaceutical Sciences, unpublished results.
4 O. Mitsunobu, Synthesis, 1981, 1.
5 A. A. Lamola, Photochem. Photobiol., 1968, 7, 619; Pure Appl. Chem.,
1970, 24, 599; G. J. Fisher and H. E. Johns, Photochemistry and
Photobiology of Nucleic Acids, ed. S. Y. Wang, Academic Press, New
York, 1976, vol. 1, p. 226.
6 W. Oppolzer and T. Godel, J. Am. Chem. Soc., 1978, 100, 2583; Helv.
Chim. Acta, 1984, 67, 1154; T. Umehara, Y. Inouye and H. Kakisawa,
Bull. Chem. Soc. Jpn., 1981, 54, 3492; H. Seto, S. Tsunoda, H. Ikeda, Y.
Fujimoto, T. Tatsuno and H. Yoshioka, Chem. Pharm. Bull., 1985, 33,
2594; J. D. Winkler, J. P. Hey and F. J. Hannon, Heterocycles, 1986, 25,
55.
7 W. Saeyens, P. Herdewijn and D. De Keukeleire, University of Gent,
Faculty of Pharmaceutical Sciences, unpublished results.
8 D. Bryce-Smith, A. Gilbert, B. Orger and H. M. Tyrrell, J. Chem. Soc.,
Chem. Commun., 1974, 334.
9 B. Sket, N. Zupancic and M. Zupan, Tetrahedron, 1986, 42, 753.
10 H. A. Neijenesch, R. J. P. J. de Ruiter, E. J. Ridderikhoff, J. O. van den
Ende, L. J. Laarhoven, L. J. W. van Putten and J. Cornelisse,
J. Photochem. Photobiol. A: Chem., 1991, 60, 325.
11 D. C. Blakemore and A. Gilbert, J. Chem. Soc., Perkin Trans. 1, 1992,
18, 2265.
In conclusion, we have observed the intriguing photoreac-
tivity of trichromophore 1 since a single, stable ortho photo-
adduct 2 arose under full chemo-, regio- and stereo-selective
control. This unprecedented reaction may imply potential cross
coupling of pyrimidine bases in nucleic acids with aromatic
amino acids in proteins or with intercalating drugs by virtue of
a [2 + 2] photocycloaddition, thereby inducing DNA alterations
which may interfere with biological function. Hitherto, it was
known that amino acids could photochemically add across the
double bond of pyrimidine bases,12 but results obtained for the
present model system may shed light on yet different photo-
chemical nucleic acids–protein and/or nucleic acids–drug
interactions.
Financial support by the Special Research Fund of the
University of Gent (project number 01109394) to D. D. K is
gratefully acknowledged.
Footnotes
† E-mail: Denis.DeKeukeleire@rug.ac.be
12 M. D. Shetlar, J. Christensen and K. Hom, Photochem. Photobiol.,
1984, 39, 125.
‡ Satisfactory spectral data for compounds 1 and 2 were obtained that were
consistent with the assigned structures and satisfactory elemental analyses
or high-resolution mass spectra were obtained. Data for 1: mp
121.5–122 °C. Rf (hexane–ethyl acetate, 7:3): 0.24. n (KBr)/cm21 1753,
Received, 23rd January 1997; Com. 7/00554G
818
Chem. Commun., 1997