Synthesis of chlorins with a distal vinyl group

Abstract

A series of chlorins containing a vinyl group on the periphery of the chlorin ring that was attached by linkers of various length, potential monomers for synthesis of polymers containing chlorin via copolymerization, was synthesized from methylpheophorbide a.Key words: methylpheophorbide a, chlorin e 6 , chlorins with a distal vinyl group, monomers for copolymerization.Porphyrins and their analogs grafted to polymers are promising photosensitizers for photodynamic sterilization of donor blood [1]. In particular, the synthesis of polymers with natural chlorins, especially the most abundant chlorophyll a and its derivatives, are of great interest. These compounds are attractive for synthesizing photosensitizers because, on one hand, they have good spectral properties and low toxicity [2] and, on the other, they have many reactive centers that enable various chemical transformations to be performed [3]. The vinyl group intrinsic to chlorophyll a and its derivatives can be used for copolymerization only with difficulty because it is bonded directly to the chlorin macrocycle and significant steric hindrances arise if it is used for the polymerization. A vinyl group distant from the macrocycle must be introduced into natural chlorin so that it can be used in copolymerization. Thus, the development of a method for synthesizing chlorins with a distal vinyl group is of great interest.Chlorophyll a itself is rarely used as starting material for chemical transformations because of its poor stability and difficulties with preparing it pure.Herein methylpheophorbide a (1), which is much more stable than chlorophyll a and is readily prepared pure while at the same time has the same reactive centers as chlorophyll a, is used as starting material for synthesizing chlorins with a vinyl group distant from the macrocycle. An allyl moiety was introduced on the periphery of the chlorin ring (4, 5, 7) by reactions at the exocycle and the 17-ester of 1. Chemical transformations were used both for introducing the vinyl group on the periphery of the chlorin ring and for introducing a reactive center distant from the macrocycle.The exocycle of chlorophyll a and its analogs, which have the same substituents in them, can be opened by primary and secondary amines [3]. This forms an amide bond at the 13-position. Substituents on the amine N atom end up bonded to the chlorin macrocycle. This reaction was used to synthesize from 1 chlorin e 6 13-amides with substituents of various hydrophilicity on the amide N atom [4,5].We synthesized chlorin e 6 13-amide (5), in which the vinyl group is bonded to the chlorin macrocycle by a 3-atom linker, by reacting 1 and allylamine. The action of certain amines on 1 is known to open the exocycle and convert the ester to an amide [5]. In this instance, this process would have been undesirable because introducing more than one distal vinyl group into chlorin could lead to formation of cross-linked polymers. The presence in the PMR spectrum of the main reaction product of singlets for the methyls of both ester...

Nanoparticles of N-Vinylpyrrolidone Amphiphilic Copolymers and Pheophorbide a as Promising Photosensitizers for Photodynamic Therapy: Design, Properties and In Vitro Phototoxic Activity

“…Reference PS—chlorin e 6 sodium salt (Ce6, Figure 1 b) was synthesized from methylpheophorbide a according to the known method [ 27 , 28 ] ( Supplementary Figure S1 ).…”

Suzuki‐Miyaura Reaction of Glycals with Base‐Labile Protecting Groups as a New Route to Glycoporphyrins

“…And on the other hand the carbohydrate moiety allows to exploit the Warburg effect and therefore intensification of the PS affinity towards cancer cells. [18,19] Despite the intensive progress in the area of glycoporphyrinoids syntheses and different approaches, [20][21][22][23][24][25][26][27][28][29][30][31] there is still need to provide new, original and versatile strategies towards them. It is probably due to the fact that general methodologies are difficult to achieve because of a very distant nature of both subunits.…”

Opening of the extra ring in pheophorbide a methyl ester by the action of amines as a one-step method for introduction of additional fragments at the periphery of chlorin macroring

“…The above requirements could be met by opening of the extra ring in pheophorbide a methyl ester (I) by the action of amines. These reactions could give rise to the corresponding chlorin e 6 13-carboxamides (Schemes 1, 2) [8][9][10][11][12][13][14][15][16][17][18]. The products of such transformations contain various fragments attached to the nitrogen atom at the periphery of the chlorin macroring; therefore, opening of the extra ring in pheophorbide a methyl ester (I) by the action of amines is successfully used to synthesize in one step chlorine e 6 13-carboxamides having various substituents at the periphery.…”