Functionalization of OEP-Based Benzochlorins To Develop Carbohydrate-Conjugated Photosensitizers. Attempt To Target β-Galactoside-Recognized Proteins

• Published in: Journal of organic chemistry Vol. 69; no. 1; pp. 158 - 172
• Main Authors: Li, Guolin, Pandey, Suresh K, Graham, Andrew, Dobhal, Mahabeer P, Mehta, Ricky, Chen, Yihui, Gryshuk, Amy, Rittenhouse-Olson, Kate, Oseroff, Allan, Pandey, Ravindra K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 09.01.2004; Amer Chemical Soc
• Subjects: Carbohydrates - chemistry; Chemistry; Chemistry, Organic; Coordination compounds; Exact sciences and technology; Galactosides - chemistry; Inorganic chemistry and origins of life; Magnetic Resonance Spectroscopy; Photosensitizing Agents - chemistry; Physical Sciences; Porphyrins - chemistry; Preparations and properties; Science & Technology; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Fast Atom Bombardment; TUMOR UPTAKE; GALECTIN-3; PHOTODYNAMIC THERAPY; BUILDING-BLOCKS; OCTAETHYLPORPHYRIN-BASED BENZOCHLORINS; COMPLEXES; PORPHYRIN DIMERS; ASYMMETRIC TRIMETHYLSILYLCYANATION; BASIC PRINCIPLES; DERIVATIVES; Copper II; Glucosamine; Nitrogen heterocycle; Sodium Tetrahydroborates; Cyanotrimethylsilane; Macrocycle; Sulfuric acid; Chemical reduction; Diisobutylaluminium hydride; Binding capacity; Functionalization; Carboxylic acid; Indium III; Carbohydrate; Chemical synthesis; Tumor cell; Magnesium bromide; In vitro; Protein; Lactose; Porphyrin; Analog; Galactose; Photosensitizer; Catalyst
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo030280b

meso-(2-Formylvinyl)octaethylporphyrin on reaction with cyanotrimethylsilane in the presence of various catalysts {copper triflate [Cu(OTf)2], indium triflate [In(OTf)3], or magnesium bromide diethyl etherate (MgBr2·Et2O)} produced a mixture of the intermediate 3-hydroxy-3-cyanopropenoporphyrin, the corresponding trimethylsilyl ether derivative, and the unexpected propenochlorins. The yields of the reaction products were found to depend on the reaction conditions and the catalysts used. The intermediate porphyrins on treatment with concentrated sulfuric acid yielded the free-base cyanobenzochlorins in major quantity along with several other novel benzochlorins as minor products. Reduction of ethyl-3-hydroxy-1-pentenoate-porphyrin with DIBAL-H/NaBH4 and subsequent acid treatment provided the corresponding free-base 103-(2-hydroxyethyl)benzochlorin, which upon a sequence of reactions gave a free-base benzochlorin bearing a carboxylic acid functionality in good yield. It was then condensed with a variety of carbohydrates (glucosamine, galactosamine, and lactosamine), and the related conjugates were screened using the galectin-binding-ability assay. Among the carbohydrate conjugates investigated, the lactose and galactose analogues displayed the galectin-binding ability with an enhancement of about 300−400-fold compared to lactose. In preliminary studies, all photosensitizers (with or without carbohydrate moieties) were found to be active in vitro [radiation-induced fibrosarcoma (RIF) tumor cells]. However, the cells incubated with lactose (known to bind to β-galactoside-recognized proteins) prior to the addition of the photosensitizers containing the β-galactose moiety (e.g., galactose and lactose) produced a 100% decrease in their photosensitizing efficacy. Under similar experimental conditions, benzochlorin without a β-galactoside moiety or the related glucose conjugate did not show any inhibition in its photosensitizing efficacy. These results in combination with the galectin-binding data indicate a possible β-galactoside-recognized protein specificity of the galactose− and lactose−benzochlorin conjugates.