Hemisynthesis of glycosylated derivatives of pheophorbide a

Abstract

Pheophorbide a is a photoactivable compound isolated from Carpinus betulus leaves EtOAc extract [1]. The photoactivable compounds, like the pheophorbide a are able to be used in photodynamic therapy. The photodynamic therapy (PDT) requires the combination of tissue oxygen, visible light and photosensitizer. Like many other photosensitizers, pheophorbide a doesn't have selectivity toward tumoral tissues [2]. To circumvent this drawback, we decided to synthesize a conjugated form of pheophorbide a with carbohydrates moieties known for their affinity to galectins [3]. These are a family of carbohydrate-binding proteins with an affinity for β-galactosides. Galectin-1 is particularly overexpressed in several tumors and plays important roles in the progression and dissemination of tumoral cells [3]. The present work details the semisynthesis of original glycosylated derivatives of pheophorbide a. Organic synthesis were monitored by analytical method including solid-phase extraction (SPE) liquid chromatography (LC) coupled with Nuclear Magnetic Resonance Spectroscopy (NMR) (LC-SPE-NMR). The combination of LC-SPE-NMR facilitated direct identification of mass-limited semisynthetic products while the isolation and purification by traditional methods failed to identify products of interest. Indeed, the semisynthesis were performed on small amounts of pheophorbide a because of the low percentage of the photosensitizer in C. betulus leaves EtOAc extract [1]. The use of LC-SPE-NMR allows a fast structure-elucidation for semisynthetic compounds present in small quantities in mixtures. MS analysis completed the data required for complete structural identification.