English

• 1.   Introduction

  Chlorophylls (Chls) are known to play important roles in light absorption and energy/electron transfer in natural photosynthesis. These excellent photofunctional abilities depend on their multi-level π-systems in the chromophore and the substituted groups along the periphery. From many quantitative structure-activity relationship (QSAR) studies it has been shown that the presence, variety and position of the substituents in the parent molecule of chlorophyll made a remarkable difference in photophysical and photobiological activity.^[1-2] Chlorophyll-a derivatives had also been applied as photosensitizers in various areas, such as artificial photosynthetic reaction centers, dye-sensitized solar cells, photodynamic therapy (PDT) and sensor devices.^[3-5] Therefore, establishing special functional groups around the porphyrin core has become an important strategy to produce useful tetrapyrrolic macrocycle compounds.^[6-8]

  Among these modifications for chlorophyll, the introduction of nitro group is a highly valued functionalization due to its triangular conjugated planar structure and strong electron-withdrawing capacity which may effectively influence and alter the basic properties of chlorins, such as electronic absorption spectrum, redox potential and S1- energy. In addition, the reduction of nitro group is a main access to amino group as one of the most important functional units in organic synthesis. The nitrification for porphyrin has also been attracted wide attention and many nitroporphyrins have demonstrated various unique properties and good application prospects.^[9-10] However, relevant reports related to chlorophyllous chlorin are scarce except our early papers and other's in which nitro group was introduced at 3- and 20-position, respectively.^[11] As a part of our research program, we report the synthesis of nitro-linked chlorins related to chlorophyll by introducing nitro group at 3-, 12-, 20- and on exocyclic ring (E-ring) based on classic chemical reaction.

  In our approach, methyl pheophorbide-a (MPa, 1), prepared from accessiable Spirulina pacifica, ^[12] was used as starting material for the synthesis of nitryl-containing chlorophyll derivatives. Firstly, methyl pheophorbide-d (MPd, 2) attaching a formyl group at 3-position was prepared by a one-pot reaction comprising an oxidation with osmium(Ⅷ) oxide and the glycol cleavage with sodium periodate. The Henry reaction of this aldehyde with nitromethane proceeded favorably in dichloromethane with TEA to afford chlorin nitro-alcohol 3 in excellent isolated yield, and subsequent dehydration was carried out initially in refluxing toluene using TsOH as catalyst to give de-esterified 3b-nitropyropheophorbide-a 4 in poor yield (4%). This Henry product 3 was refluxed in TEA, instead of acid medium, to generate chlorin 4 in 29% yield. The nitration of MPa 1 with mixed acid nitrating agent regioselectively introduced a nitro group at 20-meso-posi- tion.^[6a] The newly formed nitrated chlorin 5 (56%) converted smoothly to 20-nitropurpurin-18 6 in excellent yield through allomerization, rearrangement and anhydridisation. The Michael addition of the β-ketoester moity in pheophorbide-a 1 with 1-(4-nitrophenyl)-2-nitrothene was performed in tetrahydrofuran (THF) containing NaOCH₃ to attempting to introduce two nitro groups to the macrocycle in one step. However, the expected Michael product was so labile that it spontaneously converted to arylidene-substituted chlorin-p₆ 7 (31%) and trance amounts of pyropheophorbide-a 8 during separation at room temperature, which both consisted of two inseparable E/Z-isomers (Scheme 1).

  Scheme 1

  

  Scheme 1.  Synthesis of nitro-substituted methyl pheophorbide-a derivatives at 3- and 20-positions

  下载: 全尺寸图片 幻灯片

  Based on the above reaction results, the constructions of active reaction regions can be considered as an imperative procedure to effectively introduce nitro group. In order to establish new function structures around the exocyclic ring, methyl pyropheophorbide-a (MPPa, 9), derived from MPa 1 by a deesterification in alkali medium, was chosen as a precursor. Its allomerization in the saturated methanol solution with LiOH exposed to air gave 12-formyl substituted chlorin 10 and 13²-oxo-chlorin 11 as two major oxidative products, respectively.^[8b] The chlorin 12 with the enone moiety on the exocyclic ring also was synthesized in moderate yield by the aldol reaction of MPPa (9) with paraformaldehyde under an N₂ atmosphere in the presence of sodium methoxide (Scheme 2).

  Scheme 2

  

  Scheme 2.  Synthesis of nitro substituted methyl pheophorbide-a derivatives at 12-position and on the E-ring

  下载: 全尺寸图片 幻灯片

  Unlike MPd 2, the condensation of chlorin aldehyde 10 with nitromethane under the same condition directly generated dehydrated product 13 in 45% yield without finding the Henry product. Compared to formyl group, the Henry reaction of α-diketo group on the E-ring required a relatively rigorous reaction condition due to its lower reactivity. The analogous nitro alkylation for chlorin diketo 11 using nitromethane as nitro source was carried out by re- fluxing in TEA to form 34% nitromethylene substituted chlorin 14 in one step. In contrast to MPa 1, the chlorin 12 as an electron acceptor could also react with nitromethane in THF using sodium methoxide as catalyst to afford nitroethylated Michael adduct 15 as a pair of epimers in 58% yield (Scheme 2).

  2.   Results and discussion

  2.1   Nitration (nitroalkylation) of pheophorbide based on the Hener reaction and Michael addition

  The dehydration for Henry product 3 in refluxing toluene with TsOH was not processing smoothly and largely returned to MPd 2 with concomitant leaving of nitromethane via retro-Henry reaction. Under the acid condition (Path Ⅰ in Figure 1), the sulfonate anion as Lewis base chiefly chose to captured the hydroxylic proton with stronger acidity, rather than the weakly acidic hydrogen atom at 3b-position, while in alkaline environment (Path Ⅱ in Figure 1), like other β-nitro alcohols, ^[13] a stable intramolecular hydrogen bond was formed between the 3a-hydroxyl and the 3b-nitro group and the hydroxylic hydrogen was wrapped in the middle, making it unavailable to touch with alkalic particle in the reaction system. Consequently, the dehydration reaction of the chlorin 3 was achieved through trans-elimination along the 3a~3b bond to give desired nitrovinyl-substituted chlorin 4.

  Figure 1

  

  Figure 1.  Dehydration reaction of different Henry reaction products

  下载: 全尺寸图片 幻灯片

  The Henry reactions of chlorin 10 and 11 did not separate relevant nitroalcohols 13a and 14a, but rather their dehydrated products 13 and 14. The possible reason was that the interaction between their active protons attached to the carbon baring the nitro group with the adjacent carbonyl groups, analogous to hydroxylic hydrogen, weakened the bond energy of these C—H bonds to some extent, thus facilitating the dehydration of the nitroalcohols to directly produce nitrovinyl-substituted chlorophyll derivatives (paths Ⅲ and Ⅳ in Figure 1).

  The nucleophilic attack from both upper and lower faces in the Michael addition of chlorin ketene 12 with nitromenthane encountered different stereoscopic environment on the account of the asymmetry of chlorophyll molecule plan. The route-a approaching the E-ring from the opposite direction of the C17-propionic ester residue met with lesser steric hindrance to give the main epimer of chlorin 15, but this conjugated addition along the route-b must overcome the repulsive interaction from the long chain substituted group at 17-position to generate another epimer as secondary product.

  Analogously, the Michael addition of the MPa 1 with 1-aryl-2-nitroethylene started at the isomerization of the exocyclic ring and the formed enolic anion 1a as Michael donor could react with the electron acceptor from the both sides to produce epimers 7. The succedent nucleophilic additions to C13²-ketone group and C13¹-methoxyformyl group, caused by methoxy anion in reaction system, formed tetrahedron intermediates 1b and 1c via the route-c and route-d, respectively. The former occurred ring opening reaction by eliminating a nitromethane to rearrange to 15a-(E/Z)-arylidene-substituted chlorin-e₆ 8, while the latter converted to 13²-(E/Z)-arylidene-substituted pyropheophorbide-a 9 with concomitant the leaving of nitromethane and dimethyl carbonate (Figure 2).

  Figure 2

  

  Figure 2.  Forming process of nitroalkyl group on the exocyclic ring based on Michael addition

  下载: 全尺寸图片 幻灯片

  2.2   Optical properties of pheophorbides possessing nitro(alkenyl) group at different positions

  All the UV-vis spectra give an intense band around 400 nm, called a Soret band, and Qy bands appeared at a longest wavelength. The Qy band is accompanied with a weak vibrational band on the blue side. Between the Qy and Soret bands, less intense Qx bands are observed. The Qy and Qx bands are regulated by transition dipole moments along the molecular y- and x-axes (Scheme 1), respectively, while the Soret band based on the By and Bx bands is controlled by both the dipole moments. Therefore, the Qy and Qx bands are largely dependent on substituents attached to A-, B- and C-ring, respectively, and the Soret band is dependent on all the three substituents.

  For notroalkenylated chlorins (4, 13 and 14), the transformations from carbonyl to notroalkenyl group at the 3-, 12- and 13¹-position all induced obvious red shifts of the redmost Qy maxima (Figure 3). However, these similar modifications brought about different shift ranges toward longer wavelength, namely, 2→4 (ΔQy=8 nm), 10→13 (ΔQy=15 nm) and 11→14 (ΔQy=19 nm). In the conversion from C＝C to C＝O (9→2, 10a→10, 11b→11), ^[14] the very different Qy maxmia of the oxidized chlorins are observed in the order of 9 (ΔQy=26 nm) > 10 (ΔQy=7 nm) > 11 (ΔQy=2 nm). In terms of electronic effects, the same conjugated structures, attached to the end of the molecular y-axe, should have a similar impact on the extension of π-system of chromophore. But as far as spatial factor is concerned the differences between these reaction sites are evident. Therefore, the relevant effects of substituents on the visible spectra also are regulated by the surrounding stereo structures of the functional groups at 3-, 12- and 13¹-positions (Figure 4).

  Figure 3

  

  Figure 3.  Comparative electronic absorption spectra of 1, 4, 13 and 14

  All the spectra are normalized at Qy maxima

  下载: 全尺寸图片 幻灯片

  Figure 4

  

  Figure 4.  Substitutent effect on the Qy maxima at different positions on the chlorin periphery

  下载: 全尺寸图片 幻灯片

  The conjugation of the C＝O double bond at 12- or C13¹-position with the chromophore encounters a steric hindrance from the adjacent carbonyl group. The nonbonding orbitals of the C12-formyl group of 10 are close to the ones of the E-ring carbonyl group. The mutual repulsion between them deflects the C12-formyl group away from the macrocyclic plane along the C12－C12a bond axis and weakens their π-electron delocalization. The C13¹-carbonyl group in 11 endures a more crowded spatial environment, due to that it is located on the rigid exocyclic ring and adjacent to the keto-carbonyl group at 13²-posi- tion. The C3-formylation of chlorin 9, however, is not subjected to the influence from analogous steric hindrance, thus causing a significant red shift at the Qy band. On the contrary, the nitroalkenylations of chlorins 10 and 11 contribute to a large prolongation at their Qy maximum, comparing with same reaction for chlorin 2. Although the nitroalkenyl moiety is sterically bulkier than the correspond carbonyl group, the spatial repulsion between them is not increased but reduced due to the orientation of the nitro group which is away from other functional group (Figure 4A). The resulting increment of Qy maximum (ΔQy) benefits from the disappearance of the stereo repulsive force between the adjacent carbonyl groups, apart from the extension of π-conjugated system by establishing nitroalkenyl structure.

  The 20-nitrochlorin 5 shows a red-shifted Qy absorption band at 680 nm, moving to the red side for 14 nm (ΔQy) compared with MPa 1. However, the same nitrification at 3b, 12b and 13²a-position bring about a more long-distance shift toward longer wavelength, namely, 9→4 (ΔQy=34 nm), 10a→13 (ΔQy=23 nm) and 11b→14 (ΔQy=21 nm). In fact, the plane of the C20-nitro group and the chlorin ring are perpendicular to each other, and its substitution effect on the Qy maxima is carried out by the hyperconjugation between the carbon-oxygen σ-bonds with the chromophore π-system (Figure 4B). In addition, the shift of Qy maxima dependent upon the 20-substituent is primarily due to its factor steric. The sterically bulkier nitro group disturbs the chlorin π-plane and decreases the difference between HOMO and LUMO energy levels, ^[15] leading to a bathochromic shift of the longest wavelength absorption band (Qy maxima).

  3.   Conclusions

  The nitration and nitroalkylation of chlorins related to chlorophyll were accomplished making use of original active moieties and newly-established aldehyde or ketone group around the periphery based on electrophilic substitution, Michael addition and Henry reaction. The nitro group was introduced in different regions including at 3-, 12-, 20-position and on the exocyclic ring, respectively, to afford a series of unreported nitro-linked chlorophyll derivatives. The Soret and Q-absorption bands of the nitrated chlorins were closely related to the substituted sites of the nitro groups due to its triangular conjugated planar structure and strong electron-withdrawing capacity. These nitrations of chlorophyll derivatives and subsequent structural conversion of nitro group provided a more extensive synthetic route for acquiring novel tetrapyrrole macrocycle compounds with potential application prospect.

  4.   Experimental section

  4.1   General

  The UV-vis spectra were taken with a Unicam SP 800 spectrophotometer. The ¹H NMR spectra were recorded with a Varian 400 spectrometer. Mass spectra were recorded by a JMX-DX300 at eV. The elemental analyses were performed on a Perkin-Elmer 240 microanalyzer. Methyl pheophorbide-a (1) was obtained according to Smith's method.^[12] All chemical reagents were purchased from Merck, Fluka and Aldrich chemical companies and purified by using standard methods.

  4.2   Synthesis of methyl pheophorbide-d (2)

  To a THF solution (15 mL) of MPa (1) (186 mg, 0.307 mmol), 0.5 mL of pyridine and osmium(Ⅷ) oxide (85 mg, 0.334 mmol) in 2 mL of THF were added at 0 ℃, respectively. After stirring for 30 min at the same temperature, the reactive system was heated to room temperature and stirred for an additional hour. To the resultant mixture, an excess of a solution of sodium hydrogen sulfite (15 g) in 50% MeOH was added and stirred for 20 min. After filtering out the brown osmium(Ⅳ) oxide precipitate, CH₂Cl₂ (20 mL) and water (20 mL) were added to the mixture. The organic layer was separated and dried over anhydrous Na₂SO₄. The solvent was removed to give the solid material that was suspended in a mixture of THF (15 mL) and silica gel (2.5 g). On the treatment with a solution of sodium periodate (1 g) in water (15 mL), the color of the solution changed from green to bronze within 30 min. After adding CH₂Cl₂ (20 mL), the mixture was filtered through cotton wool and then the resultant crude material was chromatographed on silica gel with hexane-ethyl acetate (V:V=3:1) as eluent to give 161 mg of 2 (0.264 mmol, 86%) as dark red solid. The analytical data were consistent with the ones in the literature.^[16]

  4.3   Synthesis of methyl 3(R/S)-3-(1'-hydroxyl-2'-ni- troethyl)-3-devinylpheophorbide-a (3)

  To a dichloromethane solution (15 mL) of MPd 2 (128 mg, 0.211 mmol), excess nitromethane (3 mL) and TEA (2 mL) were added sequentially and stirred at room temperature under nitrogen atmosphere for 5 h. The resultant mixture was poured into cool water and extracted with dichloromethane (15 mL×3). The combined extracts were washed with water, dried over anhydrous Na₂SO₄, and treated with CH₂N₂ for short time (approximately 2 min). After evaporation in vacuo, the residue was purified on chromatograph on a silica gel column with hexane-ethyl acetate (V:V=5:1) to give 72 mg of 3 (0.107 mmol, 51%) as black solid. UV-vis (CH₂Cl₂) λ_max (relative intensity): 410 (1.00), 506 (0.13), 536 (0.13), 608 (0.05), 666 (0.32) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.53 (9.54), 9.44 (9.45), 8.5 (8.58) (each s, 3H, meso-H), 6.85 (6.83) (dd, J=13.4, 3.4 Hz, 1H, 3a-H), 6.20 (6.16) (s, 1H, 13²-H), 5.43 (5.41) (dd, J=13.4, 5.6 Hz, 1H, 3b-H), 4.89 (4.88) (d, J=13.4 Hz, 1H, 3b-H), 4.47 (q, J=7.0 Hz, 1H, 18-H), 4.21~4.14 (m, 1H, 17-H), 3.62 (q, J=7.6 Hz, 2H, 8a-H), 3.89 (3.88), 3.62 (3.61), 3.60 (3.58), 3.40, 3.21 (3.20) (each s, each 3H, CH₃+OCH₃), 2.65~2.48 (m, 2H, 17a+17b-H), 2.35~2.16 (m, 2H, 17a+17b-H), 1.79 (t, J=7.6 Hz, 3H, 8a-CH₃), 1.72 (d, J=7.2 Hz, 3H, 18-CH₃), 0.02 (br s, 1H, NH), -2.02 (br s, 1H, NH); EI-MS m/z: 669.3 (M+H⁺). Anal. calcd for C₃₆H₃₈N₅O₈: C 64.66, H 5.73, N 10.47; found C 64.49, H 5.67, N 10.37.

  4.4   Synthesis of methyl trans-3b-nitropyropheo- phorbide-a (4)

  An anhydrous TEA (20 mL) of chlorin 3 (114 mg, 0.171 mmol) was refluxed for 5 h. The mixture was poured into cool water and extracted with dichloromethane (15 mL×3), the combined extracts were washed with water, dried over anhydrous Na₂SO₄, and treated with CH₂N₂ for short time (approximately 2 min). After removing solvent in vacuo, the residue was purified on chromatograph on a silica gel column with hexane-ethyl acetate (V:V=4:1) to give 29 mg 4 (0.049 mmol, 29%) as black green solid. The title compound can also be prepared from MPPd as described in the literature.^[11c] UV-vis (CH₂Cl₂) λ_max (relative intensity): 383 (1.00), 428 (0.66), 523 (0.13), 563 (0.14), 702 (0.67) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.37 8.76, 8.58 (each s, 3H, meso-H), 8.76 (d, J=13.5 Hz, 1H, 3a-H), 7.55 (d, J=13.5 Hz, 1H, 3b-H), 5.30 (d, J=19.7 Hz, 1H, 13²-H), 5.14 (d, J=19.7 Hz, 1H, 13²-H), 4.71~4.30 (m, 1H, 18-H), 4.51~4.19 (m, 1H, 17-H), 3.67, 3.57, 3.10, 3.01 (each s, each 3H, CH₃+OCH₃), 3.51 (q, J=7.6 Hz, 2H, 8a-H), 2.80~2.61 (m, 2H, 17a+17b-H), 2.43~2.26 (m, 2H, 17a+17b-H), 1.86 (d, J=7.4 Hz, 3H, 18-CH₃), 1.63 (t, J=7.6 Hz, 3H, 8a-CH₃), 0.41 (br s, 1H, NH), -2.49 (br s, 1H, NH); EI-MS m/z: 594.3 (M+H⁺). Anal. calcd for C₃₄H₃₅N₅O₅: C 68.79, H 5.94, N11.80; found C 68.91, H 6.06, N 11.69.

  4.5   Synthesis of methyl 20-nitropheophorbide-a (5)

  To a dichloromethane solution (50 mL) of MPa 1 (212 mg, 0.350 mmol), 0.2 mL of concentrated nitric acid in acetic acid (5 mL) was added and violently stirred at 0 ℃ under nitrogen atmosphere for 2 h. The mixture was poured into cool water (50 mL), washed with 5% NaHCO₃, extracted with dichloromethane (20 mL×2). The combined extracts was washed with water, dried over anhydrous Na₂SO₄, and evaporated to dryness under vacuum. The residue was purified on chromatography on a silica gel column with hexane-ethyl acetate (V:V=4:1) to give 128 mg of 5 (0.196 mmol, 56%) as red solid. UV-vis (CH₂Cl₂) λ_max (relative intensity): 412 (1.00), 476 (0.05), 510 (0.08), 542 (0.12), 624 (0.07), 680 (0.48) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.61, 9.56 (each s, 3H, meso-H), 7.87 (dd, J=17.8, 11.5 Hz, 1H, 3a-H), 6.29 (d, J=11.6 Hz, 1H, cis-3b-H), 6.20 (s, 1H, 13²-H), 6.18 (dd, J=17.6, 1.1 Hz, 1H, trans-3b-H), 4.81~4.72 (m, 1H, 17-H), 4.16 (dd, J=8.4, 3.5 Hz, 1H, 17-H), 3.91, 3.68, 3.53, 3.19, 3.17 (each s, each 3H, CH₃+OCH₃), 3.62 (q, J=7.6 Hz, 2H, 8a-H), 2.82~2.42 (m, 2H, 17a+17b-H), 2.24~2.03 (m, 2H, 17a+17b-H), 1.67 (t, J=7.6 Hz, 3H, 8a-CH₃), 1.53 (d, J=7.2 Hz, 3H, 18-CH₃), -1.92 (br s, 1H, NH), -1.96 (br s, 1H, NH); EI-MS m/z: 651.4 (M+H⁺). Anal. calcd for C₃₆H₃₆N₅O₇: C 66.45, H 5.58, N 10.76; found C 66.51, H 5.49, N 10.63.

  4.6   Synthesis of 20-nitropurpurin-18 methyl ester (6)

  To a THF solution (25 mL) of chlorin 5 (107 mg, 0.164 mmol), an aqueous solution (5 mL) of LiOH (1.2 g) and methanol (15 mL) were sequentially added. This mixture was violently stirred in open system in dark for 3 h, poured into cool water, adjusted to pH 3 with diluted hydrochloric acid and then extracted with dichloromethane (25 mL×2). The combined extracts were washed with water, dried over anhydrous Na₂SO₄ and treated with CH₂N₂ for short time (approximately 3 min). After evaporation, the residue was purified on chromatography on a silica gel column with hexane-ethyl acetate (V:V=5:1) to give 73 mg of 6 (0.117 mmol, 71%) as red solid. UV-vis (CH₂Cl₂) λ_max (relative intensity): 438 (1.00), 530 (0.10), 578 (0.07), 656 (0.08), 709 (0.36) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.58, 9.52 (each s, 3H, meso-H), 7.82 (dd, J=17.8, 11.6 Hz, 1H, 3a-H), 6.27 (dd, J=11.6 Hz, 1.4 1H, cis-3b-H), 6.13 (dd, J=17.8, 1.4 Hz, 1H, trans-3b-H), 5.20 (dd, J=9.2, 2.6 Hz, 1H, 17-H), 4.81 (q, J=7.2 Hz, 1H, 18-H), 3.78, 3.58, 3.50, 3.16 (each s, each 3H, CH₃+OCH₃), 3.62 (q, J=7.6 Hz, 2H, 8a-H), 2.82~2.72 (m, 1H, 17a+17b-H), 2.42~2.28 (m, 1H, 17a+17b-H), 2.06~192 (m, 2H, 17a+17b-H), 1.66 (t, J=7.6 Hz, 3H, 8a-CH₃), 1.55 (d, J=7.2 Hz, 3H, 18-CH₃), -0.11 (br s, 1H, NH), -1.53 (br s, 1H, NH); EI-MS m/z: 624.3 (M+H⁺). Anal. calcd for C₃₄H₃₃N₅O₇: C 65.48, H 5.33, N 11.23; found C 65.51, H 5.44, N11.19.

  4.7   Synthesis of (E/Z)-15a-p-nitrophenylidenechlo- rin-p₆ trimethyl ester (7) and methy 13² (E/Z)-13²-p- ntrophenylidenepyropheophorbide-a (8)

  MPa 1 (208 mg, 0.343 mmol) and 1-(4-nitrophenyl)- 2-nitroethene (136 mg, 0.701 mmol) were dissolved in THF (20 mL), and a solution of sodium methoxide in methanol (1 mol/L, 4 mL) was added, then the reaction mixture was stirring at room temperature under N₂ atmosphere for 5 h. The pH value of the reaction mixture was adjusted to 4~5 by adding diluted hydrochloric acid, then extracted with dichloromethane. The combined organic layers were washed with water, dried over Na₂SO₄, and evaporated in vacuo. The residue was separated on silica gel column with hexane-ethyl acetate (V:V=5:1) to give 82 mg of 7 (0.107 mmol, 31%) as dark green solid and 7 mg of 8 (0.010 mmol, 3%) as dark green solid.

  7: UV-vis (CH₂Cl₂) λ_max (relative intensity): 413 (1.00), 502 (0.07), 531 (0.06), 611 (0.05), 664 (0.21) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.69, 9.55 (9.65), 8.70 (8.79) (each s, 3H, meso-H), 8.63 (s, 1H, 15a-CHAr), 7.99 (7.84) (dd, J=18.0, 12.0 Hz, 1H, 3a-H), 7.68 (7.39) (d, J=8.4 Hz, 2H, Ph-H), 7.31 (6.47) (d, J=8.4 Hz, 2H, Ph-H), 6.29 (6.31) (d, J=18.0 Hz, 1.4 1H, trans-3b-H), 6.10 (6.11) (d, J=12.0 Hz, 1H, cis-3b-H), 4.44 (q, J=7.2 Hz, 1H, 18-H), 4.01 (d, J=8.0 Hz, 1H, 17-H), 3.73 (q, J=7.6 Hz, 2H, 8a-H), 4.06 (3.89) 3.75, 3.55, 3.51 (3.45), 3.39 (3.43), 3.25 (3.29) (each s, each 3H, CH₃+OCH₃), 2.18~2.05 (m, 2H, 17a+17b-H), 1.88~1.55 (m, 2H, 17a+17b-H), 1.69 (t, J=7.6 Hz, 3H, 8a-CH₃), 1.01 (d, J=7.2 Hz, 3H, 18-CH₃), 0.62 (br s, 1H, NH), -1.47 (br s, 1H, NH); EI-MS m/z: 772.5 (M+H⁺). Anal. calcd for C₄₄H₄₅N₅O₈: C 68.47, H 5.88, N 9.07; found C 68.56, H 6.01, N 9.19; 8: UV-vis (CH₂Cl₂) λ_max (relative intensity): 417 (1.00), 530 (0.19), 572 (0.17), 619 (0.19), 677 (0.83) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.50 (9.56), 9.40 (9.38), 8.73 (8.58) (each s, 3H, meso-H), 8.19 (8.10) (s, 1H, 13²-CHAr), 7.98 (7.96) (dd, J=17.6, 11.2 Hz, 1H, 3a-H), 8.13 (7.65) (d, J=8.4 Hz, 2H, Ph-H), 7.57 (7.45) (d, J=8.4 Hz, 2H, Ph-H), 6.30 (6.28) (d, J=17.6 Hz, 1.4 1H, trans-3b-H), 6.18 (6.17) (d, J=11.6 Hz, 1H, cis-3b-H), 4.90 (4.02) (d, J=8.4 Hz, 1H, 17-H), 4.59 (4.32) (q, J=7.2 Hz, 1H, 18-H), 3.63 (q, J=7.6 Hz, 2H, 8a-H), 3.66 (3.76), 3.62 (3.44), 3.45 (3.40), 3.20 (each s, each 3H, CH₃+OCH₃), 2.83~2.66 (m, 2H, 17a+17b-H), 2.35~2.44 (m, 1H, 17a+17b-H), 2.12-2.00 (m, 1H, 17a+17b-H), 1.95 (1.82) (d, J=7.2 Hz, 3H, 18-CH₃), 1.68 (1.70) (t, J=7.6 Hz, 3H, 8a-CH₃), -0.25 (br s, 1H, NH), -1.88 (br s, 1H, NH); EI-MS m/z: 682.4 (M+H⁺). Anal. calcd for C₄₁H₃₉N₅O₅: C 72.23, H 5.77, N 10.27; found C 72.31, H 5.60, N 10.24.

  4.8   Synthesis of methyl pyropheophorbide-a (9)

  MPa 1 (212 mg, 0.350 mmol) was dissolved in 5% aqueous solution of pyridine (15 mL) and refluxed under nitrogen atmosphere for 5 h. The resultant mixture was poured to cool water, extracted with dichloromethane (20 mL×2). The combined organic layers were washed with water, dried over Na₂SO₄, and evaporated to dryness in vacuum. The residue was separated on silica gel column with hexane-ethyl acetate (V:V=5:1) to give 140 mg of 9 (0.256 mmol, 73%) as dark green solid. The analytical data were consistent with the ones in the literature.^[12]

  4.9   Synthesis of methyl 12-formyl-12-demethylpy- ropheophorbide-a (10) and methyl 13²-oxopheopyro- phorbide-a (11)

  To a THF solution (25 mL) of MPPa 9 (660 mg, 1.203 mmol), an aqueous solution (25 mL) of LiOH (1300 mg) and methanol (50 mL) was sequentially added. This mixture was violently stirred in open system in dark for 3 h, poured into cool water, adjusted pH to 3~4 with 5% hydrochloric acid, and then extracted with dichloromethane (80 mL×2). The combined extracts were washed with water, dried over anhydrous Na₂SO₄, and treated with CH₂N₂ for short time (approximately 3 min). After evaporation in vacuo, the residue was purified on chromatograph on a silica gel column with hexane-ethyl acetate (V:V=3:1) to give 142 mg of 10 (0.253 mmol, 21%) as green solid and 196 mg of 11 (0.349 mmol, 29%) as yellow solid. Their analytical data were consistent with the ones in the literature.^[14a]

  4.10   Synthesis of methyl 13²-methylenepyropheo- phorbide-a (12)

  MPPa 9 (421 mg, 0.767 mmol) was dissolved in THF (20 mL) and para-formaldehyde (400 mg) was added while stirring. To the solution was successively added a solution of sodium methoxide in methanol (1 mol/L, 4 mL) followed by stirring under N₂ atmosphere at room temperature for 6 h. The resulting solution was acidized with diluted HCl (40 mL) and extracted with dichloromethane (20 mL×3). The organic layers were combined and concentrated in vacuo. The residue was dissolved in dichloromethane and treated with diazomethane to convert the carboxylic acid back into methyl ester. After chromato- graphy on silica gel with hexane-ethyl acetate (V:V=3:1) as an eluent to give 323 mg 12 (0.576 mmol, 75 %) as dark yellow solid. UV-vis (CH₂Cl₂) λ_max (relative inten- sity): 412 (1.00), 433 (0.86), 525 (0.11), 560 (0.08), 616 (0.08), 675 (0.49) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.58, 9.47, 8.71 (each s, 3H, meso-H), 8.01 (dd, J=17.8, 11.6 Hz, 1H, 3a-H), 6.81 (s, 1H, 13²a-H), 6.52 (s, 1H, 13²a-H), 6.30 (dd, J=17.8, 1.1 Hz, 1H, trans-3b-H), 6.18 (d, J=11.6, 1.1 Hz, 1H, cis-3b-H), 4.65 (d, J=9.2 Hz, 1H, 17-H), 4.56 (q, J=7.4 Hz, 1H, 18-H), 3.68 (q, J=7.6 Hz, 2H, 8a-H), 3.73, 3.65, 3.44, 3.23 (each s, each 3H, CH₃+OCH₃), 2.75~2.62 (m, 2H, 17a+17b-H), 2.37~2.30 (m, 1H, 17a+17b-H), 2.10~1.98 (m, 1H, 17a+17b-H), 1.85 (d, J=7.4 Hz, 3H, 18-CH₃), 1.69 (t, J=7.6 Hz, 3H, 8a-CH₃), -0.11 (br s, 1H, NH), -1.97 (br s, 1H, NH); EI-MS m/z: 561.4 (M+H⁺). Anal. calcd for C₃₅H₃₆N₄O₃: C 74.98, H 6.47, N 9.99; found C 75.02, H 6.51, N 9.97.

  4.11   Synthesis of methyl 12-(trans-2'-nitrovinyl)-12- demethylmethylenepyropheophorbide-a (13)

  Chlorin 10 (137 mg, 0.244 mmol) was dissolved in TEA (5 mL) and excess nitromethane (3 mL) was added while stirring followed by stirring under nitrogen atmosphere at room temperature for 4 h. The resultant mixture was poured into cool water and extracted with dichloromethane (15 mL×3). The combined extracts were washed with water, dried over anhydrous Na₂SO₄, and treated with CH₂N₂ for short time (approximately 3 min). After evaporation in vacuo, the residue was purified on chromatograph on a silica gel column with hexane-ethyl acetate (V:V=4:1) to give 67 mg of 13 (0.110 mmol, 45%) as black solid. UV-vis (CH₂Cl₂) λ_max (relative intensity): 407 (1.00), 600 (0.20), 660 (0.26), 704 (0.33) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.07 (d, J=12.9 Hz, 1H, 12a-H), 8.76, 8.53, 8.19 (each s, 3H, meso-H), 7.77 (dd, J=17.8, 11.6 Hz, 1H, 3a-H), 7.55 (d, J=12.9 Hz, 1H, 12b-H), 6.23 (d, J=17.8 Hz, 1H, trans-3b-H), 6.17 (d, J=11.6 Hz, 1H, cis-3b-H), 4.99 (d, J=19.7 Hz, 1H, 13²-H), 4.83 (d, J=19.7 Hz, 1H, 13²-H), 4.26 (q, J=7.0 Hz, 1H, 18-H), 4.05 (d, J=9.6 Hz, 1H, 17-H), 3.27 (q, J=7.6 Hz, 2H, 8a-H), 3.66, 3.25, 2.98 (each s, each 3H, CH₃+OCH₃), 2.64~2.52 (m, 1H, 17a+17b-H), 2.40~2.32 (m, 1H, 17a+17b-H), 2.23~2.03 (m, 2H, 17a+17b-H), 1.81 (d, J=7.2 Hz, 3H, 18-CH₃), 1.47 (t, J=7.6 Hz, 3H, 8a-CH₃), 0.07 (br s, 1H, NH), -0.11 (br s, 1H, NH). Anal. calcd for C₃₅H₃₅N₅O₅: C 69.41, H 5.82, N 11.56; found C 69.53, H 5.90, N 11.51.

  4.12   Synthesis of methyl 13¹-(trans-2'-nitromethy- lene)-13¹-deoxo-13²-oxopyropheophorbide-a (14)

  Chlorin 11 (143 mg, 0.254 mmol) was dissolved in TEA (5 mL) and excess nitromethane (3 mL) was added while stirring followed by refluxing under nitrogen atmosphere at room temperature for 3 h. The resultant mixture was poured into cool water and extracted with dichloromethane (15 mL×3). The combined extracts were washed with water, dried over anhydrous Na₂SO₄, and treated with CH₂N₂ for short time (approximately 3 min). After evaporation in vacuo, the residue was purified on chromatograph on a silica gel column with hexane-ethyl acetate (V:V= 4:1) to give 52 mg 14 (0.086 mmol, 34%) as black solid. UV-vis (CH₂Cl₂) λ_max (relative intensity): 397 (1.00), 697 (0.33) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.68, 8.91, 8.16 (each s, 3H, meso-H), 9.50 (s, 1H, 13²a-H), 8.03 (dd, J=17.8, 11.6 Hz, 1H, 3a-H), 6.30 (d, J=17.8 Hz, 1H, trans-3b-H), 6.21 (d, J=11.6 Hz, 1H, cis-3b-H), 5.10 (d, J=9.6 Hz, 1H, 17-H), 4.62 (q, J=7.2 Hz, 1H, 18-H), 3.60 (q, J=7.6 Hz, 2H, 8a-H), 3.60, 3.56, 3.47, 3.22 (each s, each 3H, CH₃+OCH₃), 2.83~2.65 (m, 2H, 17a+17b-H), 2.42~2.27 (m, 1H, 17a+17b-H), 2.10~1.99 (m, 1H, 17a+17b-H), 1.87 (d, J=7.2 Hz, 3H, 18-CH₃), 1.64 (t, J=7.6 Hz, 3H, 8a-CH₃), 0.15 (br s, 1H, NH), -2.18 (br s, 1H, NH); EI-MS m/z: 606.4 (M+H⁺). Anal. calcd for cC₃₅H₃₅N₅O₅: C 69.41, H 5.82, N 11.56; found C 69.39, H 5.77, N 11.39.

  4.13   Synthesis of methyl 13²(R/S)-13²-(2'-nitroeth- yl)pyropheophorbide-a (15)

  Chlorin 12 (182 mg, 0.325 mmol) and excess nitromethane (5 mL) were dissolved in THF (15 mL), after a solution of sodium methoxide in methanol (1 mol/L, 4 mL) was added. The resultant reaction mixture was stirring at 35 ℃ under N₂ atmosphere for 2 h, poured to cool water and extracted with dichloromethane (15 mL×3). The combined organic layers were washed with water, dried over Na₂SO₄, and evaporated in vacuo. The residue was separated on silica gel column with hexane-ethyl acetate (V:V=4:1) to give 117 mg of 15 (0.188 mmol, 58%) as black solid. UV-vis (CH₂Cl₂) λ_max (relative intensity): 412 (2.769), 508 (0.085), 538 (0.068), 610 (0.064), 668 (0.342) nm; ¹H NMR (400 MHz, CDCl₃) δ: 9.20 (9.18), 8.92 (8.90), 8.47 (each s, 3H, meso-H), 7.63 (dd, J=17.6, 11, .2 Hz, 1H, 3a-H), 6.04 (d, J=18.6 Hz, 1H, trans-3b-H), 5.95 (d, J=11.2 Hz, 1H, cis-3b-H), 5.41 (d, J=6.8 Hz, 1H, 13²-H), 4.95 (4.94) (q, J=7.2 Hz, 1H, 18-H), 4.69~4.59 (m, 1H, 17-H), 4.38 (d, J=6.8 Hz, 1H, 13²b-H), 4.37 (d, J=6.0 Hz, 1H, 13²b-H), 3.32 (q, J=7.2 Hz, 2H, 8a-H), 3.63, 3.57, 3.22, 2.87 (2.86) (each s, each 3H, CH₃+OCH₃), 3.48~3.65 (m, 1H, 13²a-H), 3.26~3.10 (m, 1H, 13²a-H), 2.62~2.50 (m, 1H, 17a+17b-H), 2.27~2.18 (m, 1H, 17a+17b-H), 2.00~1.89 (m, 2H, 17a+17b-H), 1.89 (d, J=6.8 Hz, 3H, 18-CH₃), 1.52(t, J=7.2 Hz, 3H, 8a-CH₃), 0.28 (br s, 1H, NH), -1.82 (br s, 1H, NH); EI-MSm/z: 622.3 (M+H⁺). Anal. calcd for C₃₆H₃₉N₅O₆: C 69.55, H 6.32, N 11.26; found C 69.67, H 6.42, N 11.31.

  Supporting Information ¹H NMR spectra of the new compounds. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

  
  
• 1. [1]

     (a) Ali, H.; Vanlier, J. E. In Handbook of Porphyrin Science, Vol. 4, Eds.: Kadish, K. M.; Smith, K. M.; Guilard, R., World Scientific Publishing Company, Singapore, 2010, p. 1.
     (b) Ethirajan, M.; Patel, N. J.; Pandey, R. K. In Handbook of Porphyrin Science, Vol. 4, Eds.: Kadish, K. M.; Smith, K. M.; Guilard, R., World Scientific Publishing Company, Singapore, 2010, p. 249.
     (c) Gil, M.; Bieniaszl, M.; Seshadri, M.; Fisher, D.; Ciesielski, M. J.; Chen, Y.; Pandey, R. K.; Kozbor, D. Brit. J. Cancer. 2011, 103(10), 1.

  2. [2]

     (a) Pandey, S. K.; Zheng, X.; Morgan, J.; Missert, J. R.; Liu, T.-H.; Shibata, M.; Bellnier, D. A.; Oseroff, A. R.; Henderson, B. W.; Dougherty, T. J.; Pandey, R. K. Mol. Pharm. 2007, 4, 448.
     (b) Li, J.; He, N.; Liu, Y.; Zhang, Z.; Zhang, X.; Han, X.; Gai, Y.; Liu, Y.; Yin, J.; Wang, J. Dyes Pigm. 2017, 146, 189.
     (c) Jiang, Q.-Y.; Zhang, Z.; Liu, Y.; Yao, N.-N.; Wang, J.-J. Chin. J. Org. Chem. 2017, 37, 1814(in Chinese). (姜齐永, 张珠, 刘洋, 姚楠楠, 王进军, 有机化学, 2017, 37, 1814.)

  3. [3]

     (a) Wang, J.-J. Chin. J. Org. Chem. 2005, 25, 1353(in Chinese). (王进军, 有机化学, 2005, 25, 1353.)
     (b) Ethirajan, M.; Joshi, P.; William, W. H.; Ohkubo, K.; Fukuzumi, S.; Pandey, R. K. Org. Lett. 2011, 8, 1956.
     (c) Bellnier, D. A.; Greco, W. R.; Loewen, G. M.; Nava, H.; Oseroff, A. R.; Pandey, R. K.; Tsuchida, T.; Dougherty, T. J. Cancer. Res. 2003, 63, 1806.

  4. [4]

     (a) Ethirajan, M.; Chen, P.; Ohulchanskyy, T. Y.; Goswami, L. N.; Gupta, A.; Srivatsan, A.; Dobhal, M. P.; Missert, J. R.; Prasad, P. N.; Kadish, K. M. Chem. Eur. J. 2013, 19, 6670.
     (b) Pandey, R. K.; Goswami, L. N.; Chen, Y.; Gryshuk, A.; Missert, J. R.; Oseroff, A.; Dougherty, T. J. Lasers Surg. Med. 2006, 467, 445.
     (c) Tamiaki, H.; Wada, A.; Matsubara, S. J. Photochem. Photobiol. A. Chem. 2018, 353, 581.

  5. [5]

     (a) Pandey, S. K.; Zheng, X.; Morgan, J.; Missert, J. R.; Liu, T.-H.; Shibata, M.; Bellnier, D. A.; Oseroff, A. R.; Henderson, B. W.; Dougherty, T. J.; Pandey, R. K. Mol. Pharm. 2007, 4, 448.
     (b) Kozyrey, A. N.; Chen, Y.-H.; Goswami, L. N.; Tabaczynaki, W. A.; Pandey, R. K. J. Org. Chem. 2006, 71, 1949.
     (c) Duan, S.; Dall'Agnese, C.; Chen, G.; Wang, X.-F.; Tamiaki, H.; Yamamoto, Y.; Ikeuchi, T.; Sasaki, S. ACS Energy Lett. 2018, 3, 1708.

  6. [6]

     (a) Wang, L.-M.; Wang, Z.; Yang, Z.; Jin, Y.-X.; Wang, J.-J. Chin. J. Org. Chem. 2012, 32, 2154(in Chinese). (王鲁敏, 王振, 杨泽, 金英学, 王进军, 有机化学, 2012, 32, 2154.)
     (b) Liu, Y.; Xu, X.-S.; Li, J.-Z.; Yin, J.-G.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2014, 34, 552(in Chinese). (刘洋, 徐希森, 李家柱, 殷军港, 祁彩霞, 王进军, 有机化学, 2014, 34, 552.)
     (c) Gao, N.; Li, J.-Z.; Li, Y.-L.; Wang, Z.; Wang, J.-J. Chin. Chem. Lett. 2016, 27, 789.
     (d) Wu, H.-Q.; Wang, X.-M.; Liu, Y.; Zhao, Y.; Shim, Y.-K.; Yoon, I.; Xu, X.-M.; Li, J.-Z. Bull. Korean Chem. Soc. 2020, 41, 504.

  7. [7]

     (a) Wang, J.-J.; Wang, P.; Li, J.-Z.; Jakus, J.; Shin, Y.-K. Bull. Korean Chem. Soc. 2011, 32, 3473.
     (b) Wang, L.-M.; Wang, P.; Liu, C.; Jin, Y.-X.; Wang, J.-J. Chin. J. Org. Chem. 2012, 32, 1700(in Chinese). (王鲁敏, 王朋, 刘超, 金英学, 王进军, 有机化学, 2012, 32, 1700.)
     (c) Ji, J.-Y.; Yin, J.-G.; Zhang, Q.; Liu, C.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2014, 34, 2047(in Chinese). (纪建业, 殷军港, 张千, 刘超, 祁彩霞, 王进军, 有机化学, 2014, 34, 2047.)
     (d) Shoji, S.; Nomura, Y.; Tamiaki, H. Tetrahedron 2020, 76, 131130.

  8. [8]

     (a) Li, J.-Z.; Zhang, P.; Yao, N.-N.; Zhao, L.-L.; Wang, J.-J.; Shim, Y.-K. Tetrahedron Lett. 2014, 55, 1086.
     (b) Liu, Y.; Wu, H.; Zhang, X.; Pan, Q.; Wang, X.-M.; Peng, W.; Yin, J.-G.; Li, G.-Z.; Li, J.-Z.; Wang, J.-J. Chem. Pap. 2018, 72, 1389.
     (c) Wang, J.-J.; Li, J.-Z.; Jakus. J.; Shim, Y. K. J. Porphyrins Phthalocyanines 2012, 16, 122.
     (d) Takahashi, T.; Ogasawara, S.; Shinozaki, Y.; Tamiaki, H. Bull. Chem. Soc. Jpn. 2020, 93, 467.
     (e) Zhang, Z.; Xu, X.; Li, Y.; Li, J.; Wang, J. Chin. J. Org. Chem. 2018, 38, 2993(in Chinese). (张珠, 徐希森, 李彦龙, 李家柱, 王进军, 有机化学, 2018, 38, 2993.)

  9. [9]

     (a) Silva, A. M. G.; Tomé, A. C.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. Synlett 2002, 1155.
     (b) Richeter, S. B.; Jeandon, C.; Gisselbrecht, J.-P.; Graff, R.; Ruppert, R.; Callot, H. J. Inorg. Chem. 2004, 43, 251.

  10. [10]

      (a) Richeter, S.; Hadj-aissa, A.; Taffin, C.; van der Lee, A.; Leclercq, D. Chem. Commun. 2007, 2148.
      (b) Mandoj, F.; Nardis, S.; Pudi, R.; Lvova, L.; Fronczek, F. R.; Smith, K. M.; Prodi, L.; Genovese, D.; Paolesse, R. Dyes Pigm. 2013, 99, 136.

  11. [11]

      (a) Xu, X.-S.; Yao, N.-N.; Liu, Y.; Yin, J.-G.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2014, 34, 938(in Chinese). (徐希森, 姚楠楠, 刘洋, 殷军港, 祁彩霞, 王进军, 有机化学, 2014, 34, 938.)
      (b) Wang, Z.; Yang, Z.; Liu, Y.; Xu, X.-S.; Qi, C.-X.; Wang, J.-J. Chin. J. Org. Chem. 2012, 32, 2300(in Chinese). (王振, 杨泽, 刘洋, 徐希森, 祁彩霞, 王进军, 有机化学, 2012, 32, 2300.)
      (c) Tamiaki, H.; Ohata, M.; Kinoshita, Y.; Machida, S. Tetrahedron 2014, 70, 1629.

  12. [12]

      Smith, K. M.; Gogg, D. A.; Simpson, D. J. J. Am. Chem. Soc. 1985, 107, 4946. doi: 10.1021/ja00303a021

  13. [13]

      (a) Doyle, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2007, 107, 5713.
      (b) Shi. M.; Chen, L.-H.; Li, C.-J. Chem. Rev, 2005, 127, 3790.
      (c) Inokuma, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc, 2006, 128, 9413.
      (d) Jung, C. K.; KrisChe, M. J. J. Am. Chem. Soc, 2006, 128, 17051.

  14. [14]

      (a) Li, J.-Z.; Cui, B.-C.; Wang, J.-J.; Shim, Y.-K. Bull. Korean Chem. Soc. 2011, 32, 2465.
      (b) Zhang, S.-G. M.S. Thesis, Yantai University, Yantai, 2015 (in Chinese). (张善国, 硕士论文, 烟台大学, 烟台, 2015.)

  15. [15]

      Kureishi, Y.; Tamiaki, H. J. Porphyrins Phthalocyanines 1998, 2, 159. doi: 10.1002/(SICI)1099-1409(199803/04)2:2<159::AID-JPP62>3.0.CO;2-Q

  16. [16]

      韩光范, 王进军, 瞿燕, 沈荣基, 有机化学, 2006, 26, 43. http://sioc-journal.cn/Jwk_yjhx/CN/Y2006/V26/I01/43Han, G.-F.; Wang, J.-J.; Qu, Y.; Shim, Y.-K. Chin. J. Org. Chem. 2006, 26, 43. http://sioc-journal.cn/Jwk_yjhx/CN/Y2006/V26/I01/43

• 

  Scheme 1  Synthesis of nitro-substituted methyl pheophorbide-a derivatives at 3- and 20-positions

  下载: 全尺寸图片 幻灯片
  

  Scheme 2  Synthesis of nitro substituted methyl pheophorbide-a derivatives at 12-position and on the E-ring

  下载: 全尺寸图片 幻灯片
  

  Figure 1  Dehydration reaction of different Henry reaction products

  下载: 全尺寸图片 幻灯片
  

  Figure 2  Forming process of nitroalkyl group on the exocyclic ring based on Michael addition

  下载: 全尺寸图片 幻灯片
  

  Figure 3  Comparative electronic absorption spectra of 1, 4, 13 and 14

  All the spectra are normalized at Qy maxima

  下载: 全尺寸图片 幻灯片
  

  Figure 4  Substitutent effect on the Qy maxima at different positions on the chlorin periphery

  下载: 全尺寸图片 幻灯片
•