摘要：

CO2Me NH N N HN O CO2Me NH N N HN O Me Me Me Me Me Et Me Me Me 1 2 5 10 15 20 131 132 133 Synthesis of verdinochlorins: a new class of long-wavelength absorbing photosensitizers Andrei N. Kozyrev,a James L. Alderfer,b Thomas J. Doughertya and Ravindra K. Pandey*a a Chemistry Section, Department of Radiation Biology, Division of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA b The Department of Biophysics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA Reaction of 132-oxopyropheophorbide a with CH2N2 produced three isomeric methoxyverdinochlorins via expansion of the cyclopentanedione ring E; these long-wavelength absorbing verdinochlorins represent the first example of verdins with a reduced pyrrolic ring system, and their structural assignments have been made on the basis of 1H NMR studies; a mechanism of verdinochlorin formation is discussed.Verdins are a special class of green porphyrins 1 with a fused cyclohexenone ring system, which are obtained by the oxidation of the cyclohexanoneporphyrins or rhodins 2 under acidic reaction conditions.1 Verdin's conjugated exocyclic ring has a strong electron-withdrawing effect and causes a dramatic change in the electronic spectrum, with a prominent absorption near 690 nm.2 Due to their intense green color, Fischer named this class of compounds as ‘verdins’ (from Latin verdo = green).1 The chemistry of rhodins and verdins was further explored by Clezy, who prepared a variety of porphyrins with fused exocyclic rings.3 The utility of this class of compounds as photosensitizers for the treatment of cancer by photodynamic therapy (PDT) was demonstrated by Morgan et al.4 Recently, we have discovered a new and simple method for the preparation of 132-oxopyropheophorbide a 3 by LiOHpromoted allomerization of pyropheophorbide a.5 The oxopyropheophorbide a initially obtained as the carboxylic acid was readily converted into the corresponding methyl ester 3 by treating briefly with CH2N2.However, if a large excess of CH2N2 was used and the reaction mixture was left at room temperature for 4–6 h, a mixture of three main compounds was obtained. These were separated into individual components by preparative TLC. The most mobile orange band had a longwavelength absorption at lmax 777 nm (29% yield), the second band was red in color (lmax 747 nm, yield: 26%) and the most polar compound was isolated as a green band with lmax 739 nm (yield: 15%) (Scheme 1).Significant bathochromic shifts in the electronic absorption spectra indicated the presence of a conjugated electron-withdrawing exocyclic ring system. Mass spectral analyses of all three products gave the same molecular ion at m/z 590. Thus, compared to chlorin 3 an increase in mass by 28 daltons is observed. It has been shown that CH2N2 reacts with cyclic a-diketones,6 e.g. croconic acid, to produce trimethoxyp- benzoquinone by an unusual ring expansion.Under these reaction conditions, we anticipated the possibility of CH2 insertion into the diketocyclopentane ring of chlorin 3, which would yield the product(s) with fused cyclohexenone rings, named here as verdinochlorins (i.e. verdin with a reduced pyrrole ring). The structural assignments of the predicted reaction products were confirmed by extensive 1H NMR studies (Fig. 1). The 1H NMR spectra revealed that, compared to starting diketochlorin 3, all these compounds had an additional signal at d 4.2, integrating for three protons, along with an additional singlet at d 6.1 (for the chlorins having absorptions at 738 and 747 nm), and d 6.85 (for the chlorin absorbing at lmax 777 nm) for the olefinic proton of the cyclohexenone ring, suggesting that all three products were structural isomers.The 2D ROESY NMR data further provided valuable information for the final structural identification. In the NMR spectrum, the orange band (lmax 777 nm) showed the most lowfield shifted signal of the proton at position 131 of the cyclohexenone ring, suggesting a closer proximity to the chlorin macrocycle.This was further confirmed by ROESY experiments whic

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