15592-17-3

Upstream product

• 186581-53-3 diazomethane 
• 15664-29-6 pheophorbide-a 
• 5594-30-9 methylpheophorbide a 
• 67-56-1 methanol 
• 77-78-1 dimethyl sulfate 
• 5111-05-7 act-purpurin 5 dimethyl ester 
• 124-41-4 sodium methylate 
• 603-17-8 pheophytin a 
• 19660-77-6 chlorin e6 
• 74-88-4 methyl iodide 
• 5594-30-9 pheophorbide a methyl ester 
• 107-10-8 propylamine 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 5594-30-9 pheophorbide a methyl ester 

Downstream Products

• 19660-77-6 chlorin e6 
• 6453-67-4 methyl pyropheophorbide a 
• 5594-30-9 pheophorbide a methyl ester 
• 24533-72-0 pyropheophorbide a 
• 5111-07-9 purpurin-18-methyl ester 

Relevant academic research and scientific papers

Synthesis of new derivatives of protoporphyrin IX and chlorophyll a

The vinyl groups in protoporphyrin IX and chlorophyll a derivatives were selectively transformed into hydroxymethyl and acetoxymethyl substituents. The reactivities of β-hydroxymethyl and β-acetoxymethyl groups in porphyrins and chlorins toward nucleophilic reagents were compared for the first time using the reaction with acetylacetone as an example. Peripheral acetylacetone moieties in porphyrins and chlorins were shown to be promising as building blocks for generation of exo heterocyclic structures.

Syntheses and cellular investigations of 173-, 152-, and 131-amino acid derivatives of chlorin e6

A series of amino acid conjugates of chlorin e6, containing lysine or aspartic acid residues in positions 173, 152, or 131 of the macrocycle were synthesized and investigated as photosensitizers for photodynamic therapy of tumors. All three regioisomers were synthesized in good yields and in five steps or less from pheophytin a (1). In vitro investigations using human carcinoma HEp2 cells show that the 15 2-lysyl regioisomers accumulate the most within cells, and the most phototoxic are the 131 regioisomers. The main determinant of biological efficacy appears to be the conjugation site, probably because of molecular conformation. Molecular modeling investigations reveal that the 173-substituted chlorin e6 conjugates are L-shaped, the 152 and 131 regioisomers assume extended conformations, and the 131 derivatives are nearly linear. It is hypothesized that the 131-aspartylchlorin e6 conjugate may be a more efficient photosensitizer for PDT than the commercial currently used 15 2 derivative.

Syntheses of water-soluble cationic porphyrins and chlorins

Reactions of vinylchlorins and vinylporphyrins with N,N-dimethylmethyleneammonium iodide ('Eschenmoser's Reagent') gives Mannich adducts in which substitution (with CH2NMe2) has taken place on the terminal carbon of the vinyl group to yield a trans-3-(N,N-dimethylaminomethyl)prop-1-enyl derivative. Under no circumstances was meso substitution observed. Use of zinc(II) vinylchlorins or zinc(II) vinylporphyrins afforded the corresponding zinc(II) trans-vinyl adducts at a significantly faster rate than the metal-free substrates. Reaction of Eschenmosers reagent with deuteroporphyrin-IX dimethyl ester (29) (which possesses two peripherally unsubstituted positions) produces the bis-(N,N-dimethylaminomethyl) product (30). Treatment of the dimethylamino chlorins and porphyrins with methyl iodide, in all cases, gives an excellent yield of the corresponding quaternary ammonium iodides, and these compounds are highly water-soluble.

Design, synthesis, and in vitro photodynamic activities of benzochloroporphyrin derivatives as tumor photosensitizers

Novel benzochloroporphyrin derivatives (BCPDs) were designed, synthesized, and characterized. In vitro dark cytotoxicity and photodynamic efficacy of BCPDs were evaluated by MTT assay on human hepatoma BEL-7402 cells. The experimental results showed that BCPDs 15, 16, 17, and 18 have strong long wavelength absorptions around 670 nm and exhibit significantly lower dark cytotoxicity than BPDMA and possess potent photocytotoxicity, IC50 values 1.32 μg/mL for 15, 0.26 μg/mL for 16, 0.47 μg/mL for 17 of 0.27 μg/mL for 18, and 0.23 μg/mL for BPDMA. Among them, BCPDs 16 and 18 are more effective and promising PDT photosensitizers based on the studies with BEL-7402 cells and show nearly the same photodynamic efficacy as BPDMA. MG-P staining qualitative analysis also indicated that PDT with BCPDs 16 can induce apoptosis in BEL7402 cells.

Mono-(L)-aspartylchlorin-e6

Mono-(l)-aspartylchlorin-e6 (also known as Talaporfin, NPe6, MACE, and most recently LS-11) is a potent sensitizer for photodynamic therapy that is currently undergoing clinical trials. Using a combination of unambiguous partial synthesis from pheophytin-a and methyl pheophorbide-a, NMR spectroscopy, and single crystal X-ray diffraction, the structure of mono-(l)-aspartylchlorin-e6 is definitively shown to be the isomer in which the aspartyl residue is attached at the 152-side chain position. This conclusion is contrary to earlier assumptions, but affirms the conclusions of a study based on NMR spectroscopy; a rationale for the unique formation of the 152-aspartyl derivative is proposed.

S,S-Chiral Linker Induced U Shape with a Syn-facial Sensitizer and Photocleavable Ethene Group

There is a major need for light-activated materials for the release of sensitizers and drugs. Considering the success of chiral columns for the separation of enantiomer drugs, we synthesized an S,S-chiral linker system covalently attached to silica with a sensitizer ethene near the silica surface. First, the silica surface was modified to be aromatic rich, by replacing 70% of the surface groups with (3-phenoxypropyl)silane. We then synthesized a 3-component conjugate [chlorin sensitizer, S,S-chiral cyclohexane and ethene building blocks] in 5 steps with a 13% yield, and covalently bound the conjugate to the (3-phenoxypropyl)silane-coated silica surface.?We hypothesized that the chiral linker would increase exposure of the ethene site for enhanced?1O2-based sensitizer release. However, the chiral linker caused the sensitizer conjugate to adopt a U shape due to favored 1,2-diaxial substituent orientation; resulting in a reduced efficiency of?surface loading.?Further accentuating the?U shape was π–π stacking between the?(3-phenoxypropyl)silane and sensitizer. Semiempirical calculations and?singlet oxygen luminescence?data provided deeper insight into the sensitizer's orientation and release. This study has lead to insight on modifications of surfaces for drug photorelease and can help lead to the development of miniaturized photodynamic devices.

Chlorophyllin derivatives as photosensitizers: Synthesis and photodynamic properties

Two new photosensitizers (PSs) derived from copper-chlorophyllin were designed to have excitation wavelengths appropriate for the use in photodynamic therapy (PDT) and to have amphiphilic character with positive charge, which favors binding to cell membranes and walls and the intracellular localization in mitochondria. Herein we describe the synthesis and characterization of several properties of these two new PS, i.e., photophysical (absorption, fluorescence and singlet oxygen emission quantum yields, Ff and F?, respectively), physical-chemical (aggregation) and photobiological (binding, incorporation and cell killing). As expected, the aggregation affected not only the absorption spectra but also lowered considerably the values of φf and φΔ, which could be controlled by the interaction of the PS with aqueous micelles. In vitro studies were performed in cells, mitochondria, and vesicles to determine uptake, membrane binding, cytotoxicity, phototoxicity, and intracellular localization. The positively charged derivatives showed to be considerably more efficient for cell killing than methylene blue.

Functionalization of chlorin e6 trimethylester towards potential amphiphilic photosensitizers for photodynamic therapy

Chlorins (dihydroporphyrins) are considered, due to their ideal photophysical properties, as attractive photosensitizers for photodynamic therapy (PDT) of cancer and other therapeutic and diagnostic applications. Chlorophyll a, as a naturally occurring chlorin, forms an almost unlimited renewable resource for preparation of potential biologically active chlorin photosensitizers and fluorescence markers. To achieve amphiphilic photosensitizers which might be selectively enriched in tumor cells, we addressed linkage of per se lipophilic chlorophyll derivatives with carbohydrate based hydrophilic aminopolyols.

Chlorin e6 131:152-anhydride: A key intermediate in conjugation reactions of chlorin e6

Since the patent for the photodynamic therapy agent Talaporfin (mono-L-aspartylchlorin e6) was issued in 1987, confusion has existed regarding which of the three carboxylic acid groups in the chlorophyll degradation product, chlorin e6/su

Protonation-deprotonation equilibria in tetrapyrroles Part 3. Mono-and diprotonations of the trimethyl esters of chlorin e6 and the 71-acetal of rhodin g7 in methanolic hydrochloric acid

Spectrophotometric protonation titrations were performed for the trimethyl esters (TME) of chlorin e6 (31,32- didehydrorhodochlorin-15-acetic acid) and the 71-acetal of rhodin g7 (31,32-didehydrorhodochlorin-7 1-oxo-15-acetic acid) using HCl as the acid and methanol as the solvent. For rhodin g7 TME, the 71-acetal formation could be clearly detected as the first step in the titration. Only two spectroscopically different protonated species were observed for each chlorin derivative in addition to the neutral forms. The two protonated species were assigned to the monocation and dication of each chlorin derivative. The following pKa values were obtained: pK3 = 4.63 and pK 4 = 0.62 for chlorin e6 TME and pK3 = 4.40 and pK4 = 0.60 for the acetal of rhodin g7 TME. The protonation titration for chlorin e6 TME with HCl in acetic acid afforded UV-vis spectra similar to those obtained with HCl in methanol. The UV-vis spectrometric parameters are given for the neutral forms of chlorin e6 TME, rhodin g7 TME and its 71-acetal, as well as for the mono- and diprotonated species of chlorin e6 TME and rhodin g7 TME acetal. The protonation titration results of the chlorin e6 derivatives are compared with those previously obtained for phytyl/methyl pyropheophorbide a.