2
196
V. Yu. Pavlov et al.
LETTER
In summary, the first and highly efficient synthesis of a-
amino phosphonates 5–8 bearing porphyrin nucleus is re-
ported. The final step of constructing 5–8 was accom-
plished regioselectively in excellent yield within a few
(24) (a) Grinstein, M. J. Biol. Chem. 1947, 167, 515.
b) Caughey, W. S.; Alben, J. O.; Fujimoto, W. Y.; York, J.
(
L. J. Org. Chem. 1966, 31, 2631.
(
25) Preparation of Photoprotoporphyrins 1,2:
Porphyrin 9 (7.083 g, 12.000 mmol) was dissolved in
CH Cl (2 l) and placed into a 2.5 L two-necked flask fitted
minutes by utilizing domestic oven and CdI as a catalyst
2
2
2
thus unambiguously demonstrating the advantages of this
method in comparison with conventional procedures. We
are currently investigating the flexibility of this method
for obtaining novel a-amino phosphonates by means of
varying formylporphyrins, amines and phosphites. Bio-
logical studies of 5–8 are also underway. The results will
be reported in due course.
with oxygen inlet and effective condenser. Stream of O was
2
passed slowly through the mixture for 40 min. The solution
was irradiated for 22 h by using two high-pressure mercury
lamps with total capacity of 1.9 kW. Further repeated
1
6
chromatography on alumina with gradient elution [Et O/
2
CH Cl , 3–12% (v/v)] finally provided 1 (2.391 g, 32%) and
2
2
2
(2.244 g, 30%) with recovery of unreacted 9 (2.124 g,
3
0%).
1
Photoprotoporphyrin IX Dimethyl Ester 1: H NMR (400
MHz, CDCl ): d = 10.13–10.12 (d, 1 H, CHO, J = 6.2 Hz),
3
Acknowledgment
9
.63, 9.62, 8.29, 7.64 (all s, 4 H, meso-H), 7.98–7.90 (dd,
Jtrans = 17.7 Hz, Jcis = 11.3 Hz, 1 H, 8-CH=CH ), 6.25–6.21
The authors are grateful to Sergei V. Shorunov (N. D. Zelinsky In-
stitute of Organic Chemistry, Russian Academy of Sciences, Mos-
cow, Russian Federation) for carrying out microanalytical analyses.
2
(
dd, Jgem = 0.3 Hz, 1H, trans-8-CH=CH ), 6.15–6.12 (dd, 1
2
H, cis-8-CH=CH ), 6.07–6.05 (d, 1 H, 3-CHCHO), 4.37–
2
4
2
.12 (m, 4 H, 2 × CH CH CO CH ), 3.71 and 3.70 (2 s, 6 H,
2
2
2
3
× CH CH CO CH ), 3.38, 3.28 and 2.78 (all s, 9 H, 3 ×
2
2
2
3
References
CH -ring), 3.27–3.18 (m, 4 H, 2 × CH CH CO CH ), 1.47
3
2
2
2
3
(
s, 3 H, 2-CH ), –3.64 and –3.99 (2 br s, 2 H, 2 × NH).
3
(
1) Sternberg, E. D.; Dolphin, D.; Brückner, C. Tetrahedron
998, 54, 4151.
+
MS (ESI ): 623.4 [C H N O + H]. UV–VIS (CHCl ):
3
6
38
4
6
3
1
l
(e) = 395 (88700), 422 (81800), 570 (13100), 610
max/nm
(
(
(
(
(
(
2) Ali, H.; van Lier, J. E. Chem. Rev. 1999, 99, 2379.
3) Mody, T. D. J. Porph. Phth. 2000, 4, 362.
4) Pandey, R. K. J. Porph. Phth. 2000, 4, 368.
5) Vallés, M. A. Afinidad 1993, 50, 469.
6) Uziel, J.; Genet, J. P. Zh. Org. Khim. 1997, 33, 1605.
7) Kafarski, P.; Lejczak, B. Phosphorus, Sulfur Silicon Relat.
Elem. 1991, 63, 193.
(
10200), 669 (37100). Anal. Calcd for C H N O : C,
36 38 4 6
69.43; H, 6.15; N, 8.99. Found: C, 69.28; H, 6.21; N, 8.90.
(
26) (a) Warburg, O. Biochem. Z. 1930, 227, 171. (b) Fischer,
H.; Seeman, C. V. Z. Physiol. Chem. 1936, 242, 133.
(
(
(
27) Sparatore, F.; Mauzerall, D. J. Org. Chem. 1960, 25, 1073.
28) Sono, M.; Asakura, T. Biochemistry 1974, 13, 4386.
29) Kenner, G. W.; Quirke, J. M. E.; Smith, K. M. Tetrahedron
(
8) (a) Giannousis, P. P.; Bartlett, P. A. J. Med. Chem. 1987, 30,
1976, 32, 2753.
1603. (b) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.;
(
30) Jackson, A. H.; Matlin, S. A.; Rees, A. H.; Towill, R. J.
Chem. Soc., Chem. Commun. 1978, 645.
Wood, J. M. J. Med. Chem. 1989, 32, 1652.
(
9) (a) Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. J. Chem.
Soc., Perkin Trans 1 1984, 2845. (b) Atherton, F. R.;
Hassal, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29.
(
(
31) Dolphin, D.; Sivasothy, R. Can. J. Chem. 1981, 59, 779.
32) Smith, K. M.; Fujinary, E. M.; Langry, K. C.; Parish, D. W.;
Tabba, H. D. J. Am. Chem. Soc. 1983, 105, 6638.
33) Preparation of 3-Formyl-8-vinyldeuteroporphyrin IX
Dimethyl Ester 3 and 8-Formyl-3-vinyldeutero-
porphyrin IX Dimethyl Ester 4:
(
(
(
10) Lukszo, J.; Kowalik, J.; Mastalerz, P. Chem. Lett. 1978,
103.
11) Hakimelahi, G. H.; Sardarian, A. R. Helv. Chim. Acta 1990,
3, 180.
12) Boduszek, B. Phosphorus, Sulfur Silicon Relat. Elem. 1996,
13, 209.
(
1
7
Photoprotoporphyrin IX dimethyl ester 1 (1.555 g, 2.500
mmol) was dissolved in CHCl –MeOH [300 mL, 1:1 (v/v)]
3
1
and NaBH (1.555 g, 41.104 mmol) was added to the
4
(
(
13) Boduszek, B. Tetrahedron 1996, 52, 12483.
14) Boduszek, B. Phosphorus, Sulfur Silicon Relat. Elem. 1999,
solution with stirring. After 10 min reaction mixture was
carefully diluted with 10% aq AcOH (400 mL) to
144-146, 433.
decompose the excess of NaBH . Stirring was continued for
4
(
(
(
15) DiNello, R. K.; Chang, C. K. In The Pophyrins, Vol. 1;
Dolphin, D., Ed.; Academic Press: New York, 1978, 289.
16) Inhoffen, H. H.; Brockmann, H. Jr.; Bliesener, C. Ann.
Chem. 1969, 730, 173.
17) Sakata, I.; Nakajima, S.; Koshimizu, K.; Takada, H.; Inui, Y.
Jpn. Pat., 08067682 A2, 1996; Chem. Abstr. 1996, 124,
1
5 min. The reaction mixture was diluted with CHCl (250
3
mL). The organic phase was washed with sat. aq solution of
NaHCO (500 mL) and then with water until pH of the water
3
phase become neutral. Organic layer was separated and
evaporated to dryness. The residue was dissolved in freshly
distilled 1,4-dioxane (200 mL) and poured into 200 mL of
dioxane containing H IO (2.945 g, 12.920 mmol). Reaction
342987.
5
6
(
18) Hikida, M.; Mori, M.; Sakata, I.; Nakajima, S.; Takata, H.
mixture was protected from light and stirred vigorously for
5 min at ambient temperature. Wet NaHCO , prepared by
PCT Int. Appl., WO 98 14453, 1998; Chem. Abstr. 1998,
4
3
128, 282741.
mixing 6 g of NaHCO with 2 mL of water, was added and
3
(
(
19) Ando, A.; Kumadaki, I. J. Fluorine Chem. 1999, 100, 135.
20) Yumita, N.; Nishigaki, R.; Sakata, I.; Nakajima, S.;
Umemura, S.-I. Jpn. J. Cancer Res. 2000, 91, 255.
21) Kabachnik, M. M.; Ternovskaya, T. N.; Zobnina, E. V.;
Beletskaya, I. P. Zh. Org. Khim. 2002, 38, 504.
stirring was continued for 5 min. Then inorganic salts were
removed on a glass filter under reduced pressure and 1,4-
dioxane was evaporated. The remaining solid was dissolved
(
(
(
in CHCl and flashed on a short column equipped with 150
3
g of alumina (Merck, 230–400 mesh, Brockmann Grade IV,
elution with 2% Et O in CHCl ) to yield 962 mg (65%) of
22) Kabachnik, M. M.; Dokichev, A. N.; Ternovskaya, T. N.;
Beletskaya, I. P. Zh. Org. Khim. 2002, 38, 508.
2
3
porphyrin 3. Following the above method, iso-photoproto-
porphyrin IX dimethyl ester 2 was converted into porphyrin
23) Kabachnik, M. M.; Zobnina, E. V.; Beletskaya, I. P. Zh. Org.
Khim. 2003, in press.
4
in 66% yield.
Synlett 2003, No. 14, 2193–2197 © Thieme Stuttgart · New York