METHOD FOR PREPARING BILIVERDIN OR DERIVATIVE THEREOF

Abstract

A method for preparing biliverdin or a derivative thereof includes applying a compound represented by formula 2 as a raw material; R is hydrogen, C.sub.1-C.sub.5 alkyl, or benzyl; “” at positions A and B independently represent a single bond or a double bond; when “” represents a single bond, R.sub.1 or R.sub.2 connected to the single bond is selected from one of tosyl, p-toluenesulfonyl, phenylsulfonyl, phenylsulfinyl; and when “” represents a double bond, R.sub.1 or R.sub.2 connected to the double bond is hydrogen.

Claims

1. A method for preparing biliverdin or a derivative thereof, the method comprising applying a compound represented by formula 2 as a raw material: ##STR00019## wherein: R is hydrogen, C.sub.1-C.sub.5 alkyl, or benzyl; “” at positions A and B independently represent a single bond or a double bond; when “” represents a single bond, R.sub.1 or R.sub.2 connected to the single bond is selected from one of tosyl, p-toluenesulfonyl, phenylsulfonyl, phenylsulfinyl; and when “” represents a double bond, R.sub.1 or R.sub.2 connected to the double bond is hydrogen.

2. The method of claim 1, wherein the biliverdin or a derivative thereof has a formula 1 as follows: ##STR00020## R is hydrogen, C.sub.1-C.sub.5 alkyl, or benzyl.

3. The method of claim 1, wherein the compound represented by formula 2 is one of the following compounds. ##STR00021##

4. The method of claim 1, wherein the biliverdin or a derivative thereof is prepared by the compound represented by formula 2 through a heating reaction.

5. The method of claim 4, wherein the heating reaction involves a solvent selected from substituted benzene, pyrrolidone, dimethyl formamide (DMF), and tetrahydrofuran (THF), or a mixture thereof.

6. The method of claim 5, wherein the solvent is selected from xylene, nitrobenzene, chlorobenzene, DMF, THF, or a mixture thereof.

7. The method of claim 4, wherein the heating reaction is performed at a temperature of 100-160° C.

8. The method of claim 1, wherein the biliverdin or a derivative thereof is prepared by the compound represented by formula 2 in the presence of a catalyst.

9. The method of claim 8, wherein the catalyst is an organic base.

10. The method of claim 9, wherein the organic base is pyridine, sodium ethoxide, or a mixture thereof.

Description

DETAILED DESCRIPTION

[0027] To further illustrate the disclosure, embodiments detailing a method for preparing biliverdin or a derivative thereof are described below. It should be noted that the following embodiments are intended to describe and not to limit the disclosure. If no specific technology or conditions are stated in the disclosure, the technology or conditions described in the related art or the product manual should be followed. Nuclear magnetic resonance (NMR) was measured using Bruker-AMX400 nuclear magnetic resonance instrument. ESI-MS was measured using Finnigan-MAT-95 mass spectrometer. All reagents are analytical pure (Sinopharm Chemical Reagent Co., Ltd.). In the following examples, 1,5-dihydro-4-methyl-3-(2-p-toluenesulfoethyl)-5-neneneba p-toluenesulfonyl-2H-2-pyrrolidone (shown in Formula 12) is prepared in reference to Chem Lett., 2001, 6, 590-591; 5-formyl-3-methoxycarbonyleth-4-methylpyrrolic acid tert butyl ester (shown in Formula 13), 9-tert-butoxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonyleth)-2-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (shown in Formula 17) are prepared in reference to Bull. Chem. Soc. Jpn., 1994, 67, 3088-3093; 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-p-tolylene sulfonyl group ethyl)-dipyrrolidone 1-one (shown in Formula 14), 9-tert-butyloxycarbonyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-p-tolylene thioethyl)-dipyrrolidone 1-one (shown in Formula 18) are prepared in reference to J. Org. Chem., 2020, 85, 13015-13028; 9-formyl-2,7-dimethyl-8-(2-methoxycarbonylethyl)-3-vinyldipyrrolidene-1-one (shown in formula 15) is prepared in reference to Angew. Chem. Int. Ed., 1998,37,13-14, 1843-1846.

Example 1

[0028] 0.92 g of compound 3,3′-(3,18-bis (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (shown in formula 3) was dissolved in 40 mL of xylene. The resulting mixture was heated to 135° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain 0.50 g of a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 63%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ1.89 (s, 3H), 2.10 (s, 3H), 2.13 (s, 3H), 2.20 (s, 3H), 2.56 (t, J=8.1 Hz, 4H), 2.95 (t, J=8.1 Hz, 4H), 3.69 (s, 6H), 5.46 (d, J=12.0 Hz, 1H), 5.66 (dd, J=12.0, 4.0 Hz, 1H), 5.68 (dd, J=16.0, 4.0 Hz, 1H), 6.02 (s, 1H), 6.08 (s, 1H), 6.14 (dd, J=16.0, 4.0 Hz, 1H), 6.51 (dd, J=16.0, 12.0 Hz, 1H), 6.64 (dd, J=16.0, 12.0 Hz, 1H), 6.81 (s, 1H); ESI-Mass: 633.20 (M+Na).sup.+.

[0029] The reaction formula is as follows:

##STR00006##

Example 2

[0030] 0.92 g of 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in formula 4) was dissolved in 40 mL of DMF. The resulting mixture was heated to 130° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 60%.

[0031] The reaction formula is as follows:

##STR00007##

Example 3

[0032] 0.92 g of compound 3,3′-(3,18-bis (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (shown in formula 3) was dissolved in 40 mL of nitrobenzene. The resulting mixture was heated to 150° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain 0.50 g of a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 61%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ1.89 (s, 3H), 2.10 (s, 3H), 2.13 (s, 3H), 2.20 (s, 3H), 2.56 (t, J=8.1 Hz, 4H), 2.95 (t, J=8.1 Hz, 4H), 3.69 (s, 6H), 5.46 (d, J=12.0 Hz, 1H), 5.66 (dd, J=12.0, 4.0 Hz, 1H), 5.68 (dd, J=16.0, 4.0 Hz, 1H), 6.02 (s, 1H), 6.08 (s, 1H), 6.14 (dd, J=16.0, 4.0 Hz, 1H), 6.51 (dd, J=16.0, 12.0 Hz, 1H), 6.64 (dd, J=16.0, 12.0 Hz, 1H), 6.81 (s, 1H); ESI-Mass: 633.20 (M+Na).sup.+.

Example 4

[0033] 0.92 g of compound 3,3′-(3,18-bis (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (shown in formula 3) was dissolved in 40 mL of pyrrolidone. The resulting mixture was heated to 135° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain 0.50 g of a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 45%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ1.89 (s, 3H), 2.10 (s, 3H), 2.13 (s, 3H), 2.20 (s, 3H), 2.56 (t, J=8.1 Hz, 4H), 2.95 (t, J=8.1 Hz, 4H), 3.69 (s, 6H), 5.46 (d, J=12.0 Hz, 1H), 5.66 (dd, J=12.0, 4.0 Hz, 1H), 5.68 (dd, J=16.0, 4.0 Hz, 1H), 6.02 (s, 1H), 6.08 (s, 1H), 6.14 (dd, J=16.0, 4.0 Hz, 1H), 6.51 (dd, J=16.0, 12.0 Hz, 1H), 6.64 (dd, J=16.0, 12.0 Hz, 1H), 6.81 (s, 1H); ESI-Mass: 633.20 (M+Na).sup.+.

Example 5

[0034] 0.92 g of compound 3,3′-(3,18-bis (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (shown in formula 3) was dissolved in 40 mL of xylene. The resulting mixture was heated to 100° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain 0.50 g of a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 51%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ1.89 (s, 3H), 2.10 (s, 3H), 2.13 (s, 3H), 2.20 (s, 3H), 2.56 (t, J=8.1 Hz, 4H), 2.95 (t, J=8.1 Hz, 4H), 3.69 (s, 6H), 5.46 (d, J=12.0 Hz, 1H), 5.66 (dd, J=12.0, 4.0 Hz, 1H), 5.68 (dd, J=16.0, 4.0 Hz, 1H), 6.02 (s, 1H), 6.08 (s, 1H), 6.14 (dd, J=16.0, 4.0 Hz, 1H), 6.51 (dd, J=16.0, 12.0 Hz, 1H), 6.64 (dd, J=16.0, 12.0 Hz, 1H), 6.81 (s, 1H); ESI-Mass: 633.20 (M+Na).sup.+.

Example 6

[0035] 0.92 g of compound 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in formula 4) was dissolved in 40 mL of DMF. The resulting mixture was heated to 160° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 49%.

Example 7

[0036] 0.92 g of compound 3,3′-(3,18-bis (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (shown in formula 3) was dissolved in 40 mL of xylene. Thereafter, 10 mL of pyridine was added as a catalyst. The resulting mixture was heated to 135° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain 0.50 g of a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 73%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ1.89 (s, 3H), 2.10 (s, 3H), 2.13 (s, 3H), 2.20 (s, 3H), 2.56 (t, J=8.1 Hz, 4H), 2.95 (t, J=8.1 Hz, 4H), 3.69 (s, 6H), 5.46 (d, J=12.0 Hz, 1H), 5.66 (dd, J=12.0, 4.0 Hz, 1H), 5.68 (dd, J=16.0, 4.0 Hz, 1H), 6.02 (s, 1H), 6.08 (s, 1H), 6.14 (dd, J=16.0, 4.0 Hz, 1H), 6.51 (dd, J=16.0, 12.0 Hz, 1H), 6.64 (dd, J=16.0, 12.0 Hz, 1H), 6.81 (s, 1H); ESI-Mass: 633.20 (M+Na).sup.+.

Example 8

[0037] 0.92 g of compound 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in formula 4) was dissolved in 40 mL of DMF. Thereafter, 10 mL of pyridine was added as a catalyst. The resulting mixture was heated to 130° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure, and the residue was recrystallized with ethyl acetate to obtain a blue-green solid, which was biliverdin diester (shown in formula 7), with a yield of 74%.

Example 9

[0038] 0.92 g of 3,3′-(3,18-bis (2-neneneba p-toluenesulfonyl ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in formula 5) was dissolved in 40 mL of anhydrous THF, and then 0.93 g of sodium tert-butoxide dissolved in 10 mL of tert-butanol was added. The resulting mixture was heated to 135° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure. The residue was mixed with water, acidified with dilute hydrochloric acid, and extracted with dichloromethane to obtain 0.50 g of a blue-green solid, which was biliverdin (shown in Formula 8), with a yield of 74%. The spectral data is consistent with the literature Monatshr Chem., 1989, 120, 575-580.

[0039] The reaction formula is as follows:

##STR00008##

Example 10

[0040] 0.77 g of 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in formula 6) was dissolved in 35 mL of anhydrous THF, and then 0.93 g of sodium tert-butoxide dissolved in 10 mL of tert-butanol was added. The resulting mixture was heated to 135° C. and stirred for 2 hours, cooled, evaporated to remove the solvent under reduced pressure. The residue was mixed with water, acidified with dilute hydrochloric acid, and extracted with dichloromethane to obtain 0.40 g of a blue-green solid, which was biliverdin (shown in Formula 8), with a yield of 69%. The spectral data is consistent with the literature Monatshr Chem., 1989, 120, 575-580.

[0041] The reaction formula is as follows:

##STR00009##

Example 11

1. Synthesis of Compound Represented by Formula 3

Synthesis of 3,3′-(3,18-bis (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (Shown in Formula 3)

[0042] ##STR00010##

[0043] 1.00 g of 9-tert-butyloxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonyl ethyl)-2-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (shown in Formula 9) was added to 10 mL of trifluoroacetic acid at 20° C. and stirred for 30 min. Thereafter, 0.87 g of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (shown in Formula 10) was added to the resulting mixture, and stirred at 35° C. for 10 hours. 20 mL of dichloromethane was added to the mixed solution. The mixed solution was neutralized with sodium bicarbonate to pH 7. The organic layer was collected, washed with saturated sodium bicarbonate to neutral, dried over anhydrous sodium sulfate, filtered, and recrystallized with ethanol to obtain 1.19 g of a blue-green solid, that is, 3,3′-(3,18-di (2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrinyl)-dimethyl dipropionate (shown in Formula 3), with a yield of 72%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.52 (s, 3H), 1.93 (s, 3H), 1.95 (s, 3H), 1.99 (s, 3H), 2.34 (s, 3H), 2.40 (s, 3H), 2.51-2.65 (m, 6H), 2.87 (t, J=7.2 Hz, 2H), 2.96 (t, J=7.2 Hz, 2H), 3.27 (t, J=7.2 Hz, 2H), 3.66 (s, 3H), 3.67 (s, 3H), 5.55 (s, 1H), 5.75 (s, 1H), 6.66 (s, 1H), 7.14 (d, J=8.0 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H); ESI-Mass: 891.34 (M+1).sup.+.

[0044] The two compounds represented by formulas 9 and 10 are synthesized as follows:

1.1) Synthesis of 9-tert-butyloxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonyl ethyl)-2-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (Shown in Formula 9)

[0045] ##STR00011##

[0046] 5.24 g of the compound represented by Formula 11 was put into a reaction flask, dissolved with 30 mL of dichloromethane, and cooled to 0° C. 2.40 g of 85% m-chloro perbenzoic acid was added in batches to the reaction flask, stirred at room temperature for 3 hours, and washed with saturated sodium bisulfite solution. The organic layer was collected, and then washed with saturated salt water, water, dried over anhydrous sodium sulfate, filtered, concentrated to obtain 4.97 g of a yellow solid, that is, 9-tert-butyloxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonyl ethyl)-2-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (shown in Formula 9), with a yield of 92%. The compound can be directly used for next reaction. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.57 (s, 9H), 2.08 (s, 3H), 2.15 (s, 3H), 2.30 (s, 3H), 2.54 (t, J=8.0 Hz, 2H), 2.80 (t, J=7.2 Hz, 2H), 3.03 (t, J=8.0 Hz, 2H), 3.17 (t, J=7.2 Hz, 2H), 3.70 (s, 3H), 6.00 (s, 1H), 7.03 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 9.89 (s, 1H), 10.20 (s, 1H); ESI-Mass: 563.25 (M+Na).sup.+.

1.2) Synthesis of 9-tert-butoxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonylethyl)-2-(2-p-toluenesulfoethyl)-dipyrrolidene-1-one (Shown in Formula 11)

[0047] ##STR00012##

[0048] Under nitrogen protection, 10.50 g of the compound having formula 12 and 14.85 g of the compound having formula 13 were mixed and dissolved in 250 mL of anhydrous THF. 16.55 g of tri-n-butylphosphorus and 6.50 g of DBU were sequentially added to the resulting mixture, stirred at room temperature for 12 hours, and then 1.0 g of solid iodine was added. The mixture was further stirred at room temperature for 12 hours and concentrated under reduced pressure. 20 mL of ethanol was added to the residue, to yield a solid. The solid was filtered, and washed with ethanol to obtain 13.60 g of a yellow solid, which is 9-tert butyloxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonylethyl)-2-(2-p-toluenesulfoethyl)-dipyrrolidene-1-one (shown in formula 11), with a yield of 73%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.56 (s, 9H), 2.07 (s, 3H), 2.13 (s, 3H), 2.28 (s, 3H), 2.54 (t, J=8.1 Hz, 2H), 2.80 (t, J=7.1 Hz, 2H), 3.03 (t, J=8.1 Hz, 2H), 3.15 (t, J=7.1 Hz, 2H), 3.70 (s, 3H), 6.00 (s, 1H), 7.03 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 9.89 (s, 1H), 10.18 (s, 1H), 10.71 (s, 1H); ESI-Mass: 446.20 (M+Na).sup.+.

1.3) Synthesis of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-2-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (Shown in Formula 10)

[0049] ##STR00013##

[0050] 5.00 g (9.3 mmol) of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-p-tolylene sulfonyl group ethyl)-dipyrrolidone 1-one (shown in Formula 14) was dissolved in 20 mL of trifluoroacetic acid, stirred at room temperature for 30 minutes, and 20 mL of trimethyl orthoformate was added, continued stirring at room temperature for 1 hour, and then water was added. The resulting mixture was extracted with dichloromethane, washed with saturated sodium bicarbonate to neutral, washed with water, dried with anhydrous sodium sulfate, filtered, concentrated and recrystallized with ethanol to obtain 2.24 g of a yellow solid, namely, 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-2-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (shown in formula 10), with a yield of 55%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.93 (s, 3H), 2.07 (s, 3H), 2.43 (s, 3H), 2.56 (t, J=7.6 Hz, 2H), 2.66-2.70 (m, 1H), 2.88-2.92 (m, 1H), 2.95-3.10 (m, 4H), 3.65 (s, 3H), 5.98 (s, 1H), 7.34 (d, J=8.0 Hz, 2H), 7.51 (d, J=8.0 Hz, 2H), 9.72 (s, 1H), 10.78 (s, 1H), 10.91 (s, 1H); ESI-Mass: 491.22 (M+Na).sup.+.

2. Synthesis of Compound Represented by Formula 4

Synthesis of 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (Shown in Formula 4)

[0051] ##STR00014##

[0052] 1.00 g of 9-tert-butyloxycarbonyl-3,7-dimethyl-8-(2-methoxycarbonyl ethyl)-2-(2-p-tolylene sulfonyl group ethyl)-dipyrrolomethen-1-one (shown in Formula 9) was added to 10 mL of trifluoroacetic acid at 20° C. and stirred for 30 min. Thereafter, 0.617 g of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonylethyl)-3-vinyl dipyrrolidene-1-one (shown in Formula 15) was added to the resulting mixture, and stirred at 35° C. for 10 hours. 20 mL of dichloromethane was added to the mixed solution. The mixed solution was neutralized with sodium bicarbonate to pH 7. The organic layer was collected, washed with saturated sodium bicarbonate to neutral, dried over anhydrous sodium sulfate, filtered, and recrystallized with ethanol to obtain 0.93 g of a blue-green solid, that is, 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in Formula 4), with a yield of 66%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.70 (s, 3H), 2.02 (s, 3H), 2.04 (s, 3H), 2.10 (s, 3H), 2.39 (s, 3H), 2.52-2.55 (m, 4H), 2.73-2.78 (m, 2H), 2.86-2.89 (m, 4H), 3.03-3.08 (m, 2H), 3.68 (s, 3H), 5.59 (d, J=17.1, 1H), 5.61 (d, J=10.5, 1H), 5.81 (s, 1H), 5.87 (s, 1H), 6.53 (dd, J=17.1, 11.6 Hz, 1H), 6.65 (s, 1H), 7.29 (d, J=8.2 Hz, 2H), 7.57 (d, J=8.2 Hz, 2H); ESI-Mass: 751.95 (M+1).sup.+.

3. Synthesis of Compound Represented by Formula 5

3,3′-(3,18-bis (2-neneneba p-toluenesulfonyl ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (Shown in in Formula 5)

[0053] ##STR00015##

[0054] 1.00 g of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonylethyl)-3-vinyldipyrrolidene-1-one (shown in Formula 15) was dissolved in 5 mL trifluoroacetic acid, stirred at 25° C. for 30 minutes, then 0.87 g of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-nenenebb p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one was added. The resulting mixture was stirred at 25° C. for 10 hours, concentrated under reduced pressure, dissolved in dichloromethane, washed saturated sodium bicarbonate to neutral. The organic layer was collected, drive over anhydrous sodium sulfate, filtered, and recrystallized with ethanol to obtain 0.91 g of a blue-green solid, with a yield of 55%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.52 (s, 3H), 1.93 (s, 3H), 1.95 (s, 3H), 1.99 (s, 3H), 2.34 (s, 3H), 2.40 (s, 3H), 2.51-2.65 (m, 6H), 2.87 (t, J=7.2 Hz, 2H), 2.96 (t, J=7.2 Hz, 2H), 3.27 (t, J=7.2 Hz, 2H), 3.66 (s, 3H), 3.67 (s, 3H), 5.55 (s, 1H), 5.75 (s, 1H), 6.66 (s, 1H), 7.14 (d, J=8.0 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H); ESI-Mass: 945.34 (M+Na).sup.+.

[0055] The two compounds represented by formulas 15 and 16 are synthesized as follows:

2.1) Synthesis of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (Shown in Formula 16)

[0056] ##STR00016##

[0057] 5.56 g (10.0 mmol) of 9-tert-butyloxycarbonyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (shown in Formula 17) was dissolved in 20 mL of trifluoroacetic acid, stirred at room temperature for 30 minutes, and 20 mL of trimethyl orthoformate was added, continued stirring at room temperature for 1 hour, and then water was added. The resulting mixture was extracted with dichloromethane, washed with saturated sodium bicarbonate to neutral, washed with water, dried with anhydrous sodium sulfate, filtered, concentrated and recrystallized with ethanol to obtain 2.24 g of a yellow solid, namely, 9-formyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (shown in Formula 16), with a yield of 50%. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.93 (s, 3H), 2.07 (s, 3H), 2.43 (s, 3H), 2.56 (t, J=7.6 Hz, 2H), 2.66-2.70 (m, 1H), 2.88-2.92 (m, 1H), 2.95-3.10 (m, 4H), 3.65 (s, 3H), 5.98 (s, 1H), 7.34 (d, J=8.0 Hz, 2H), 7.51 (d, J=8.0 Hz, 2H), 9.72 (s, 1H), 10.78 (s, 1H), 10.91 (s, 1H); ESI-Mass: 507.18 (M+Na).sup.+.

2.2) Synthesis of 9-tert-butoxycarbonyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (Shown in Formula 17)

[0058] ##STR00017##

[0059] 5. 20 g of 9-tert-butyloxycarbonyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-p-tolylene thioethyl)-dipyrrolidone 1-one (shown in Formula 18) was put into a reaction bottle, dissolved with 40 mL of methanol, and then 11 g of 30% m-chloro perbenzoic acid was added. The resulting mixture was stirred at 70° C. for 5 hours, cooled, concentrated under reduced pressure, dissolved in dichloromethane, washed with saturated sodium bisulfite solution. The organic layer was collected, washed with saturated salt water and water in turn, dried over anhydrous sodium sulfate, filtered and concentrated to obtain 5.17 g of a yellow solid, namely 9-tert-butyloxycarbonyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (shown in Formula 17), with a yield of 94%, which can be directly used for next reaction. .sup.1H NMR (400 MHz, CDCl.sub.3): δ 1.55 (s, 9H), 1.93 (s, 3H), 2.08 (s, 3H), 2.42 (s, 3H), 2.58 (t, J=7.6 Hz, 2H), 2.66-2.71 (m, 1H), 2.87-2.90 (m, 1H), 2.96-3.10 (m, 4H), 3.66 (s, 3H), 5.97 (s, 1H), 7.35 (d, J=8.0 Hz, 2H), 7.53 (d, J=8.0 Hz, 2H), 9.73 (s, 1H), 10.78 (s, 1H), 10.91 (s, 1H); ESI-Mass: 579.32 (M+Na).sup.+.

4. Synthesis of Compound Represented by Formula 6

Synthesis of 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (Shown in Formula 6)

[0060] ##STR00018##

[0061] 1.00 g of 9-tert-butyloxycarbonyl-2,7-dimethyl-8-(2-methoxycarbonyl ethyl)-3-(2-neneneba p-toluenesulfonyl ethyl)-dipyrrolomethen-1-one (shown in Formula 17) was added to 10 mL of trifluoroacetic acid at 20° C. and stirred for 30 min. Thereafter, 0.617 g of 9-formyl-2,7-dimethyl-8-(2-methoxycarbonylethyl)-3-vinyldipyrrolidene-1-one (shown in formula 15) was added to the resulting mixture, and stirred at 35° C. for 10 hours. 20 mL of dichloromethane was added to the mixed solution. The mixed solution was neutralized with sodium bicarbonate to pH 7. The organic layer was collected, washed with saturated sodium bicarbonate to neutral, dried over anhydrous sodium sulfate, filtered, and recrystallized with ethanol to obtain 0.93 g of a blue-green solid, that is, 3,3′-(3-vinyl-18-(2-p-tolylene sulfonyl group ethyl)-2,7,13,17-tetramethyl-1,19-dioxo-1,19,22,24-tetrahydro-21H-8,12-porphyrin)-dipropionate dimethyl ester (shown in formula 6), with a yield of 66%.

[0062] It will be obvious to those skilled in the art that changes and modifications may be made, and therefore, the aim in the appended claims is to cover all such changes and modifications.