Porphyrins natural total synthesis

Oxidation reactions were used in the synthesis of porphyrin d, the metal-free ligand system of naturally occurring heme d,. In a total synthesis of porphyrin d,12d oxo functions were introduced into isobacteriochlorin 3 by selenium dioxide oxidation to yield 4. The selenium dioxide selectively attacks the 3- and 8-positions of the partially reduced pyrrole rings of the chromophore. In another synthesis23a c of porphyrin d, an isobacteriochlorin 5, derived by... 

The second methodology involves direct introduction of glycosylated moieties onto a suitably functionalized meso-arylporphyrin scaffold, accessible from a natural source (protoporphyrin-IX) or by total synthesis. Several O-,133,145,146 S-,147 and N-glycoporphyrins148 (125-129) have thus been prepared (Fig. 12). Moreover, in order to explore the influence of the clustered peripheral saccharides around the porphyrin scaffolds, and to evaluate their photophysical properties, the synthesis of dodecavalent porphyrins bearing four trivalent glycodendrons via amide ligation (129) has been achieved.149... 

The classic sequence of experiments with natural compounds in the twentieth century has been as follows isolation from biological sources, purification, elucidation of molecular structure, and finally total synthesis. These tasks of organic chemistry were fulfilled by the end of the century as far as the major components of higher organisms are concerned. Only compounds that are central to the growth of their tissues are the subject of this book. Many individual compounds of this kind of natural product, namely lipids, steroids, carbohydrates, carotenoids, porphyrins, vitamins, nucleic acids, and proteins, are today commercially available, and their structural and dynamic analysis has reached an accuracy and diversity that leaves little to be desired (Karrer, 1954 Fieser and Feiser, 1960 Tedder et al., 1972 Nuhn, 1981 Fuhrhop, 1982 Beyer and Walter 1988 Fuhrhop and Penzlin, 1994 Mann et al., 1994). 

Both monocyclic building blocks were prepared in a multistep reaction sequence from L-glutamic acid. In another alternative reaction sequence the succinic imide 107 as a common intermediate for rings A an B was synthesized from R-malate. The enantiomerically pure buildings blocks could be transformed along different routes with appropriate D,C pyrroles into the dimers 108 and 109 which on treatment with acid formed the desired bilinimine 110. The outlined total synthesis of porphyrin di established the absolute configuration of natural heme di. 

The first ruthenium porphyrin-catalyzed intramolecular carbenoid C - H insertion to afford selectively cis-2,3-disubstituted-2,3-dihydroergocornine using tosylhydrazone salts as the carbene source was reported by Zheng et al. [192]. This general strategy was applied in natural product synthesis to provide a route to the total synthesis of racemic epi-conocarpan. Enantio-selective synthesis of 2,3-dihydrobenzofurans was also achieved by a similar route using chiral ruthenium porphyrins as catalysts for this interesting carbon-carbon bond formation [193]. Recently, it was found that dinuclear fx-oxo osmium porphyrins are able to catalyze intermolecular carbene insertion into C - H bonds in cyclohexene [153]. 

The synthesis of porphyrins from monopyrrolic, dipyrrolic, tripyrrolic and tctrapyrrolic precursors requires, even for an experienced porphyrin chemist, a substantial amount of time and effort to accomplish. As an alternative to these total synthetic routes, nature provides a source of prefabricated porphyrins. Among the several porphyrins which can be isolated from natural material,s the red blood pigment heme, protoporphyrin dimethyl ester81 b and hemato-porphyrin, both derived from heme, are the only compounds which can be obtained in sufficient amounts. Heme is available in almost unlimited amounts from slaughter-house waste. From 1 L of blood ca. 1 g of heme can be isolated.81 b Currently, heme is offered commercially by chemical retailers at a relatively low price so that is cheaper to buy hemin than to perform a self-isolation in the laboratory. 

---