Synthesis of oxochlorins from the red blood pigment heme and their transformation into potentially biologically active chlorin derivatives

Abstract

The hydroxychlorin rac-3 was prepared from the readily accessible chlorins rac-Sa, b. The alcohol function of rac-3 could be used to attach an estrogen residue 28 and the hydroquinone 19 to yield the chlorin estrogen ethers 32a, b and the chlorin hydroquinone ether rac-30 respectively. The prepared chlorin estrogen derivatives might be useful as sensitiChlorophyll a, the green pigment of plant photosynthesis, is the prototype of the chlorin class of natural products[*] which today includes a number of compounds with differing structures and functions. The common structural unit in this class is the chlorin framework 1 with a partially saturated pyrrole ring, which arises from the completely unsaturated porphyrin. On account of their photophysical properties the chlorins resulting from this structural modifications are suitable for use as pigments in photosynthesi~ [~] and for medical applications, for example in photodynamic tumor therapy (PDT)r41.We have recently shown that chlorins like rac-2a, ruc-2b, and rac-4 can easily be derived from the red blood pigment hemeus]. In this paper we describe the further functionalization of chlorin ruc-2a by degradation of the exocyclic double bond in the 3-position. The functional group may be used to attach different residues. Artificial photosynthesis systems may thus be prepared containing "natural" chlorins as the structural units in contrast to the previously synthesized model systems based on porphyrins. The functionalized chlorin rac-3 may also be modified to provide sensitizer structures and fluorescence marked6] for photodynamic tumor therapy and other therapeuticldiagnostic applications. Synthesis of Oxochlorins and Their Further TransformationThe chlorin structure ruc-4 bearing a lipophilic heptyl side chain was recently prepared in our laboratory with respect to an application in PDT, because amphiphilic properties of sensitizers might be decisive for biological activity. The liphophilic side chain had to be introduced into the macrocycle at the very beginning of the synthesis, so that each of other possible active structures would require its individual preparative pathway. Therefore, we aimed at the synthesis of the oxochlorins mc-9 and rac-10 and the ~~~~~~~ zers and fluorescence markers for photodynamic therapy and other diagnostichherapeutic applications. The chlorin hydroquinone ether is of interest as a potential artificial photosynthesis system, which contains a "natural" chlorin as a structural subunit in contrast to previously synthesized model systems based on porphyrins.hydroxychlorin ruc-3 which have functional groups to which different residues can be attached to alter properties. Since it was expected that the chlorin chromophore could be sensitive to the oxidation conditions required for the cleavage of the exocyclic double bond we first transformed the more stable known nickelchlorin racda. b[5b1 into the

Synthetic Chlorins, Possible Surrogates for Chlorophylls, Prepared by Derivatization of Porphyrins

“…The syntheses began with the chlorins 7-H 2 5a­( E/Z ) derived from the “2-isomer” of acetyl-deuteroporphyrin IX dimethyl ester (Scheme ). , The mixture of E/Z isomers, obtained as shown in Scheme , was metalated with nickel acetylacetonate to give the nickel chelates 7-Ni5a­( E/Z ). Treatment of the latter to a series of reactions resulted in the oxochlorin 7-Ni16 where also the amide was converted to an ester.…”

“…The sequence of reactions entailed iodination of the alkene with accompanying formation of the iminium lactone (step 1), hydrolysis of the imine and hydroxide displacement of the iodide (step 2), hydrolysis of the amide, hydrolysis of the propionate esters (not shown), and elimination of acetone (step 3), oxidation of the β-hydroxypyrrole to form the oxochlorin (step 4), and methylation of the three carboxylates (step 5). The overall yield was a remarkable 55% …”

“…A route was therefore devised that avoided formation of the nickel chelate (Scheme ). Thus, chlorin 7-H 2 5a­( E/Z ) was metalated with zinc acetylacetonate, which afforded a mixture of the Z/E isomers 7-Zn5a­( E ) and 7-Zn5a­( Z ) . The mixture was treated to conditions to oxidize the exocyclic ethylidene bond and form the zinc oxochlorin, affording 7-Zn17 .…”

Tetraphenylporphyrin as a protein label for triple detection analytical systems

“…For example, the selective accumulation of porphyrins bound to monoclonal antibodies allowed for detection of cancer cells [31] . In another study conjugates with steroids were created [32] in order to initiate a localized oxidative stress and apoptosis of the cancer cells. Moreover, conjugates with mono- and polynucleotides [33] allowed for selective photo-cleavage of specific strands of DNA.…”

Design and studies of novel polyoxysterol-based porphyrin conjugates

“…They are used as photosensitizers for photodynamic therapy [3], in saccharide sensing [4][5][6][7][8][9], and anion binding [10]. Nearly all studies have been limited so far to bileacid based structures [11][12][13][14], with a few exceptions of porphyrin conjugates of estrogens [15][16][17], androgens [18,19] and cholesterol [20].…”