Synthesis of Chlorins from the Red Blood Pigment Heme Hydroxyalkylporphyrins rac‐8h, k and rac‐9h, k prepared from the readily accessible red blood pigment heme can be transformed into the geminally dialkylated chlorins rac‐10–13 upon reaction with N,N‐dimethylacetamide dimethyl acetal. The chlorins are promising candidates for application in Photodynamic Tumor Therapy (PDT). The reported synthetic method should be useful for the synthesis of natural hydroporphyrins containing geminally dialkylated structural parts.

Chlorophyll a (l), the green photosynthesis pigment, is the prototype of the chlorin class of natural products,"] which has recently been expanded to include a number of compounds ['] with differing structures, biological sources, and functions. The common structural unit in this class is the chlorin framework 2 with a partially saturated pyrrole ring, which is derived from the completely unsaturated porphyrin. The photophysical properties of the chlorins resulting from this structural modification predestine them as pigments for photosynthesisr3] and for medical applications, for example in photodynamic tumor therapy (PDT).14]The chlorin r a~-3 [~] with geminal dialkyl substitution in the saturated pyrrole ring was easily obtained from the red blood pigment heme and functionalized in the 3 position by degradation of the double bond. Artifical 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 rue-8 may be modified to provide sensitizer structures and fluorescence markersr6] for photodynamic tumor therapy and other diagnostic/therapeutic applications.Chlorin rac-3 was first complexed with zinc(1r) ions to protect the chromophore (Scheme 1). The oxidative cleavage of the exocyclic double bond and subsequent decomplexation under acidic conditions led to oxochlorin rac-7. The amide function in vac-6 was hydrolyzed readily due to the anchimeric participation of the 3-0x0 group to give rue-14. The preparation of the corresponding nickeloxochlorin rac-11 required the hydrolysis of the amide function and cleavage of the double bond by iodolactonization, followed by a retro-aldol-type fragmentation and oxidation with MnO,.r7] The X-ray structure analysis[81 of the nickeloxochlorin rac-11, which was conducted in light of the coenzyme function of metal-containing chlorins, [*g. k1

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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

A. F. M. Barton, CRC Hundbook of' Soluhility Parameters und Orher Cohesion Purarrreters, CRC Press, Boca Raton, FL, 1983. [I41 Vollstiindige Enantiomerentrennung der Carhonsiure 1 wurde durch Nutzung der selektiven Loslichkeit in Dioxan erreicht. Das uberschussige Enantiomer war in Dioxan loslich, wdhrend das Racemdt einen stahilen, unloslichen Komplex [(+)-I . Dioxan] bildete [4h].