Synthesis of potential antitumor agents, dimeric and trimeric chlorins, from methylpheophorbide a

Abstract

A series of dimeric and trimeric chlorins were synthesized from methylpheophorbide a. They are potential photosensitizers for photodynamic therapy in oncology. The macrocycles were conjugated due to the formation of ester and amide bonds. The carboxy groups were activated and catalytic transesterification was carried out to form the ester bond. The amide bond was formed using carboxy group activation; in several cases, amidation of the ester group in position 13(2) of the exocycle of methylpheophorbide а was carried out, which does not require activation.

Opening of Exocycle of the Methyl Pheophorbide a 13(2)-Amide Derivatives in a Water-Acetone Solution in the Presence Hydrochloric Acid

“…We have previously shown that the amidation of the ester group at position 13(2) of the methyl pheophorbide a exocycle is a convenient way of forming an amide bond having a significant synthetic potential. [6][7][8][9][10][11][12][13][14] The use of this reaction is a convenient way of synthesizing the conjugates of methylpheophorbide a and its analogs with terpenophenols, [6][7][8][9] introducing bulk alkyl substituents, [10,11,13] as well as obtaining dimeric and trimeric chlorophyll a derivatives. [12,14] The hydrolysis of the 17-substituent ester group in such conjugates is of interest from the viewpoint of hydrophilizing the resulting derivatives, as well as further chemical modification using the carboxyl group reactions.…”

“…The reaction occurs chemoselectively and with good yields of the target carboxylic derivatives. [7,14,15] To determine the possibility of this reaction application to the methylpheophorbide a 13-amide derivatives the conversion of analogous simple derivatives (4-8) (Scheme 2) in acetone with concentrated hydrochloric acid were studied in this paper.…”