390
0.75
587
1.0
0.5
0.0
(b)
0.50
0.25
518
489
636
678
(b)
693
(a)
(a)
0.00
500
600
l / nm
700
800
400
500
600
l / nm
700
800
Fig. 1 Electronic absorption spectra (in CH2Cl2) of (a) dioxoporphyrin 6
and (b) porphyrin 7
Fig. 2 Electronic absorption spectra (in CH2Cl2) of (a) chlorin 3 and (b) its
enolate 3a
Further purification of this complex mixture also gave a
novel chlorin (5% yield) with a significantly red shifted
absorption Qy-band at 710 nm and a Soret band at 440 nm.
Compared to 132-oxopyropheophorbide a, the 1H NMR
spectrum of this chlorin showed the presence of a distinctive
singlet for a formyl group at d 11.08 and disappearance of the
resonances for the 12-methyl protons. The mass spectrum of
this product gave a molecular ion peak at m/z 576, confirming
the replacement one of the methyl group by a formyl
evidence of enolization in 132-oxopyropheophorbide a 3 was
also confirmed by its specific UV–VIS spectrum (splitting of
the Soret band), a characteristic property of enolates in
pheophorbide system (Fig. 2). The enolic form 3a produced
under other basic conditions (KOH, NaOH) was found to be
stable in non-polar solvents. However, traces of alcohol or
water completely destroyed the potassium and sodium enolates,
while the lithium salt appeared to be quite stable.
1
substituent. The H NMR and 2D ROESY data supported the
The chemistry discussed here might explain the origin of
structure as 12-demethyl-12-formyl-132-oxopyropheophorbide
a methyl ester 8. The formation of chlorin 8 from 132-oxopyr-
opheophorbide a 3, which lacks protons at 132-position,
possibly proceeds via a vinylogous enolization involving the
methyl protons attached to the adjacent pyrrolic ring (ring C).
This process would certainly be facilitated by the presence of
strong electron-withdrawing carbonyl functions at the adjacent
cyclopentane ring. A proposed mechanism for the formation of
chlorin 8 is shown in Scheme 2. The key step in this reaction is
the formation of a reactive intermediate species 3a. Reaction of
enolate 3a with singlet oxygen, via [4 + 2] cycloaddition and
subsequent rearrangement, would generate the 12-formyl
analog 8. Chlorins in general are known to convert molecular
oxygen to singlet oxygen (1O2) on irradiating with light. In
order to further confirm the [4 + 2] cycloaddition mechanism
with singlet oxygen, we used purpurin-18 imide,4 as a more
stable substrate, which could also undergo vinylogous enoliza-
tion similar to 3a. Photooxidation of purpurin-18 imide in
aqueous LiOH–THF on exposing to sunlight produced the
corresponding 12-formyl derivative in high yield (up to 60%).
When the reaction was performed in the dark, the 12-formyl
analog was not detected.10
deoxophylloerythrioetioporphyrin (12-demethyl-DPEP),
a
minor petroporphyrin structure isolated by Callot.11
The newly discovered LiOH promoted enolization of pyr-
opheophorbide a has opened a simple and effective way for the
preparation of 132-oxopyropheophorbide a 3 which had pre-
viously been isolated as a by-product in minor quantities.6
Further studies are underway to explore the reactivity of the
cyclopentanedione ring system for the preparation of novel
chlorins with linear conjugation as photosensitizers for pho-
todynamic therapy and models for photosynthetic reaction
centers.
This work was supported by grants from Mallinckrodt
Medical Inc., St. Louis, the National Institutes of Health (CA
55791) and the Oncologic Foundation of Buffalo.
Notes and References
† E-mail: pdtctr@sc3101.buffalo.edu
1 R. Willstatter and A. Stoll, Untersuchungen uber Chlorophyll, Springer,
Berlin, 1913.
2 P. H. Hynninen, in Chlorophylls, ed. H. Scheer, CRC Press, Ann Arbor,
1991, p. 145.
3 M. R. Wasielewski, J. R. Norris, L. L. Shipman, C. P. Lin and
W. A. Svec, Proc. Natl. Acad. Sci. USA, 1981, 78, 2957.
4 A. N. Kozyrev, G. Zheng, C. Zhu, T. J. Dougherty, K. M. Smith and
R. K. Pandey, Tetrahedron Lett., 1996, 37, 6431.
Despite intensive studies in chlorophyll chemistry, this is the
first example in which this type of enolization is observed. The
5 J. K. Conant and J. F. Hyde, J. Am. Chem. Soc., 1929, 51, 3668.
6 L. Ma and D. Dolphin, J. Org. Chem., 1996, 61, 2501.
7 R. B. Woodward, W. A. Ayer, J. M. Beaton, F. Bickelhaupt, R. Bonnett,
P. Buchschacher, G. L. Closs, H. Dutler, J. Hannan, F. P. Hauck, S. Ito,
A. Langemann, E. Le Goff, W. Leimgruber, W. Lwowski, J. Sauer,
Z. Valenta and H. Volz, Tetrahedron, 1990, 46, 7599.
8 K. M. Smith, General features of the structure and chemistry of
porphyrin compounds, in Porphyrins and Metalloporphyrins, ed. K. M.
Smith, Elsevier, Amsterdam, 1975.
9 A. N. Kozyrev, G. Zheng, E. Lazarou, T. J. Dougherty, K. M. Smith and
R. K. Pandey, Tetrahedron Lett., 1997, 38, 3335.
10 A. N. Kozyrev and R. K. Pandey, unpublished results.
11 J. Verne-Mismer, R. Ocampo, C. Bauder, H. L. Callot and P. Albrecht,
Energy Fuels, 1990, 4, 639.
HN
H
N
CO2Me
N
HN
H
N
LiOH
1O2
O
O
3
Me
Me
_
–
O
O
O
O
CO2Me
N
3a
HN
H
HN
H
H
O
CHO
H
Me
Me
8
OH
O
O
O
OH
O_
CO2Me
CO2Me
Scheme 2
Received in Corvallis, OR, USA, 27th October 1997; 7/07805F
482
Chem. Commun., 1998